Print Email  

Additional Funding Descriptions

Madeline Corrigan, New Jersey Institute of Technology

  • Funding Type: Investigator Grant
  • Amount: $600,000
  • Date: 7/2016 6/2018
  • Title: Translation of an Upper Extremity Exoskeleton to Community Use for Individuals with Duchenne Muscular Dystrophy
  • Abstract: Admittance control provides a means to increase active range of motion for individuals with Duchenne muscular Dystrophy (DMD) to a greater extent than that provided by passive arm supports, devices limited to those in the earlier stages of functional loss due to imperfect gravity compensation. This project aims to translate the modular application of admittance control to the Continuum passive arm support in order to increase active range of motion for individuals with DMD.

Joshua Selsby, Ph.D., Iowa State University

  • Funding Type: Exploratory Grant
  • Amount: $199,998
  • Date: 6/2016 5/2017
  • Title: Quercetin-based therapies with immediate application for dystrophic muscle
  • Abstract: We found previously that quercetin-mediated activation of a PGC-1alpha pathway protected function and attenuated histopathological injury in dystrophic hearts but only transiently protected respiratory function in the same animals.  We propose to maximize therapeutic benefits to dystrophic cardiac and skeletal muscle by combining quercetin with Lisinopril and the orally available and safe supplement, nicotinamide riboside, as these approaches could be immediately applied to DMD patients.

Jerry Mendell, M.D., Nationwide Children’s Hospital

  • Amount: $452,181
  • Date: 4/2016 4/2017
  • Title: Determine incidence and prognosis of clinically significant cardiac, skeletal muscle and cognitive impairment in carriers of DMD and BMD
  • Abstract: This study is a collaborative project between the Neuromuscular and Cardiology divisions at Nationwide Children’s Hospital. It is a longitudinal study with baseline and 12-month follow up assessments of female carriers of DMD/BMD mutations. The testing in this study aims to determine the frequency and clinical significance of heart and extremity muscle involvement in these patients and will evaluate the emotional burden of being a carrier as well as a care provider for a child with DMD or BMD.

Lee Sweeney, Ph.D., The University of Florida

  • Funding Type: Wellstone Center
  • Amount: $525,000
  • Date: 2/2016 1/2021
  • Title: University of Florida Wellstone Muscular Dystrophy Cooperative Center
  • Abstract: Funding will be in support of a combination of GRMD dog studies and mouse imaging studies that will follow on from the most promising individual drugs and evaluate combinations of drugs. Trials in DMD patients will evaluate one drug at a time before evaluating combinations of drugs. By first studying drug combinations that emerge from our mouse studies in the dog model of DMD, we will be able to make the best decision as to which drug combinations to move into human DMD patients. These ancillary dog studies will have the additional advantage of helping us evaluate the predictive value of results from the studies in mdx/DBA mice. If the results in the mdx/DBA mice are concordant with the results in dystrophic dogs, then more reliance can be placed on the mouse model for drug development. PPMD funds can also be used to cover any charges associated with unanticipated mouse studies, including imaging studies, that may grow out of this proposal, and that exceed the budget obtained from the NIH grant. The funds will be used not only for magnet time, but for technician costs as well.

Elizabeth McNally, M.D., Northwestern University

  • Funding Type: Wellstone Center
  • Amount: $ 276,000
  • Date: 2/2016 1/2021
  • Title: Northwestern University Fellowship - Wellstone Muscular Dystrophy Cooperative Center
  • Abstract: This project proposes experiments to evaluate the effects and mechanisms by which glucocorticoid steroids alter repair and regeneration of muscle fibers in the muscular dystrophies.

Stanley Nelson, M.D., The University of California, Los Angeles

  • Funding Type: Wellstone Center
  • Amount: $ 449,000
  • Date: 2/2016 1/2021
  • Title: UCLA - Wellstone Muscular Dystrophy Cooperative Center
  • Abstract: Despite the knowledge that Duchenne muscular dystrophy (DMD) is caused by a mutation within the DMD gene, there is substantial variability in the progression of this early onset childhood disease. The mean age at which DMD boys typically lose the ability to walk independently is 10-11, but the variability is large with some boys requiring the use a wheelchair before the age of 6 while others remain ambulatory at age 20. Further some have early onset cardiomyopathy and others never develop cardiomyopathy. Data collected within ImagingDMD provides valuable information on differences in phenotypic progression particularly in regard to muscle imaging. Here we will perform whole genome sequencing to identify about 4 million DNA sequence variants in all individuals participating in Imaging DMD. These data will be searched to identify genetic correlation with imaging phenotypes. This type of variation creates opportunity to understand how natural genetic variation modulates the severity of DMD. PPMD Supplemental funding will complement the UF/Northwestern/UCLA Wellstone by providing interpreted whole genome sequence data on all subjects enrolled in ImagingDMD. Genomic DNA will be prepared from cell lines, or if no cell line available, from a blood specimen collected at an ImagingDMD study visit.

The Eureka Institute for Translational Medicine Certificate Course

  • Funding Type: Investigator Grant
  • Amount: $83,885
  • Year: 2016
  • Title: The Eureka Institute for Translational Medicine Certificate Course
  • Meeting Date(s): May 2016 and October 2016
  • Meeting Location: Sicily, Italy

New Directions in Biology and Disease of Skeletal Muscle

  • Funding Type: Meeting Grant
  • Amount: $10,000
  • Year: 2016
  • Title: New Directions in Biology and Disease of Skeletal Muscle
  • Meeting Date(s): June 29 - July 1, 2016 
  • Meeting Location: Orlando, FL
  • Meeting Goals:  This meeting brings together scientists working to understand mechanisms and develop new therapies for muscle disease, especially the muscular dystrophies. The “New Directions” meeting differs from other topically related meetings because of its focus on bringing together industry and academic attendees with a focus on evaluating laboratory based observations and assessing or testing suitability for therapy in the preclinical and clinical setting. This meeting was developed in response to MD Care Act and the recognition that devising and testing therapy for rare neuromuscular disorders requires organization and coordinated efforts among all stakeholders. In addition to the focus on identifying and testing therapeutic
    pathways, the New Directions meeting places a high emphasis on inclusion of trainees and young investigators, as it is recognized that the challenges of these medical problems will require a diverse and prolonged effort to realize cures for these devastating disorders.
    Objective 1: The presentation and sharing of unpublished data. This meeting emphasizes the presentation of unpublished work. Early access to information allows for new collaborations to form moving scientific discovery forward faster into translation.
    Objective 2: Promotion of collaboration between industry and academic investigators. As targets are increasingly moving towards development, preclinical and clinical testing, the interaction and partnership between industry and academia is increasingly important. The first session of this meeting is designed to promote industry and advocacy group participation.
    Objective 3: Clinical trial planning and outcome. We will devote a specific session to outcomes and endpoints for clinical trials for neuromuscular disease especially the muscular dystrophies and hope to contribute to improved consensus and understanding of appropriate expectations for clinical trials.
    Objective 4: Identify both common and unique targets for each muscle disease. This meeting provides a format where multiple different mechanisms of muscle disease are covered providing a backdrop to identify common elements that can be manipulated therapeutically.
    Objective 5: Provide trainees and young investigators a forum in which to present data and to encourage trainees to remain studying neuromuscular disease. Trainees are expected to present posters, and senior and junior investigators are engaged by evaluating these presentations.

TREAT-NMD Advisory Committee for Therapeutics, 13th Meeting, Barcelona, Spain, 29th April - 1st May 2016

  • Funding Type: Meeting Grant
  • Amount: $25,000
  • Year: 2016
  • Title: TREAT-NMD Advisory Committee for Therapeutics, 13th Meeting, Barcelona, Spain, 29th April - 1st May 2016
  • Meeting Date(s): 29th April - 1st May 
  • Meeting Location: Barcelona, Spain
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations thatare necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and havethe potential to be funded longer term.
    Four applications will be reviewed at the upcoming meeting, three are concerned with Duchenne Muscular Dystrophy and one is concerned with Spinal Muscular Atrophy (SMA).

    1) Development of the Hematopoetic Prostaglandin D Synthase Inhibitor, GSK3350916A, for the Treatment of Duchenne Muscular Dystrophy, GlaxoSmithKline, Pennsylvania, USA
    2) Use of simvastatin as a potential treatment for Duchenne Muscular Dystrophy, Solid Biosciences, Massachusetts, USA
    3) MKPD-1, a selective modulator of PPARdelta, for the treatment of Duchenne Muscular Dystrophy, Mitobridge Inc, Massachusetts, USA
    4)  A Phase 3, randomized, patient, investigator and sponsor-blinded, placebo-controlled multicenter, variable treatment duration study to evaluate efficacy and safety of oral LMI070 in patients with Infantile-onset Type I Spinal Muscular Atrophy, Novartis Institutes for Biomedical Research , Basel, Switzerland

International School of Biological Magnetic Resonance: 14th Course Future of Molecular Biophysics

  • Funding Type: Meeting Grant
  • Amount: $10,000
  • Year: 2016
  • Title: International School of Biological Magnetic Resonance:14th Course Future of Molecular Biophysics
  • Meeting Date(s): 7-17 MAY 2016
  • Meeting Location: Erice-Sicily
  • Meeting Goals: This course focuses on recent advances in molecular biophysics and structural biology, as applied to key problems in modern biomedical research. Lectures will cover the principles of structural biology (xTray crystallography, NMR, Electron microscopy, computation) and biophysics (spectroscopy, kinetics, singleT molecule studies), together with recent research results. The long format of the course encourages extensive discussion and life-long collaboration and friendship. Students and postdoctoral researchers from a wide range of backgrounds are encouraged to apply.

2016 NCH/OSU Myology Course (5th Annual)

  • Funding Type: Meeting Grant
  • Amount: $30,000
  • Year: 2016
  • Title: 2016 NCH/OSU Myology Course (5th Annual)
  • Meeting Date(s): Aug. 29 - Sep. 2, 2016
  • Meeting Location: Nationwide Children’s Hospital, Columbus, OH
  • Meeting Goals: The goal of this course is to provide trainees with an up-to-date and expert survey of neuromuscular diseases, and to provide them with practical experience for furthering their clinical or laboratory research career.  The expert faculty addresses clinical syndromes, mechanisms of pathogenesis, molecular therapeutics, and importantly aspects of career development. The course is available to both pre-and post-graduate trainees, and both clinical- and laboratory-based trainees are welcome.  We have structured the course so that both groups are together for morning lectures, which emphasize clinical features, molecular pathogenesis, and known and potential therapies.  In the afternoon, clinical trainees receive training in more specifically clinical activities, and laboratory trainees will take part in wet-lab activities, organized by Dr. Denis Guttridge.  At the end of each day, the groups join up again for a keynote lecture, and they gather for a banquet with faculty the evening before the course ends. The Clinical Track is primarily directed at clinical fellows (in Neuromuscular Disease; Genetics; Electrophysiology; Physical Medicine & Rehabilitation; etc.), although other specialties and levels of training are welcome, including medical students, residents in Neurology or Pediatrics, and ancillary staff (e.g., nurse practitioners, or physical therapists). The Laboratory Track is directed primarily toward graduate students and Ph.D. post-doctoral fellows who wish to learn new skills, or expand upon skill sets relevant to their work in their home laboratory.  They choose elective workshops for each afternoon led by NCH/OSU and external faculty:

Joel Schneider, Solid Ventures, LLC

  • Funding Type: Solid Ventures, LLC
  • Amount: $100,000
  • Date: 1/2015 12/2015
  • Title: Phase I Contract for Solid Suit Robotics
  • Abstract: PPMD is excited to announce a collaboration with Solid Ventures to engage SRI International in the research and development of the “Solid Suit,” a soft, wearable assistive device for people with Duchenne and Becker muscular dystrophy. Conceptually, the Solid Suit could be worn under one’s clothing next to his/her skin (picture Spiderman’s suit). It is not yet known whether the project will yield a full body suit, an upper body suit to enhance upper body function, or a lower body suit to enhance lower limb function and mobility. PPMD and Solid hope the Solid Suit will enable patients to use a device in their day-to-day activities that assists in muscle function and perhaps helps muscle preservation.

Guy Odom, University of Washington

  • Amount: $49,571.55
  • Date: 4/2016 - 4/2017
  • Title: In silico re-engineered micro-dystrophin: Expanding a novel approach to evade T-cell immune responses in DMD patients
  • Summary: A significant hurdle for DMD gene therapy is the high likelihood of an immune response against micro-dystrophin (µDys), resulting in destruction of expressing myofibers.  We seek to avoid this problem via a computational protein immuno-silencing & redesign protocol that integrates human immune epitope data, MHC epitope or antigen prediction tools & proteomic data to derive µDys proteins with highly reduced immunogenicity while retaining stability & function.  Our proof-of-principle proposal builds on preliminary data showing µDys can be redesigned to predictably immuno-silence a major human epitope while retaining function in dmd mice.

Denis Guttridge, Ohio State University

  • Amount: $48,087.90
  • Date: 6/2016 - 5/2017
  • Title: NF-kB Function in DMD Cardiomyopathy
  • Summary: Almost all DMD patients develop heart problems. In order to improve treatment, new drugs will have to work by fixing both skeletal and heart muscles. Interestingly, in contrast to DMD skeletal muscles, very little is known about a dystrophic heart. Our studies focus on a protein called NF-kappaB (NF-kB), which we showed contributes to the degeneration of skeletal muscles. We have now demonstrated that a drug that inhibits NF-kB called NBD is capable of rescuing a dysfunctional heart. In this application, we seek to understand how NF-kB is capable of causing DMD hearts to fail. Obtaining this information will provide additional insight on the how NF-kB functions in DMD and potentially ways to target this molecule to improve DMD therapy.  

Stephen Broadbent, Critical Path Institute

  • Funding Type: GIFTED
  • Amount: $900,000
  • Date: 7/2015 - 7/2018
  • Title: Duchenne Regulatory Science Consortium Research Agreement
  • Summary: The Duchenne Regulatory Science Consortium (D-RSC) was formed by Parent Project Muscular Dystrophy and the Critical Path Institute in order to develop tools to accelerate therapy development for this urgent unmet medical need, aiming to accelerate and improve trial protocol development and reduce the numbers of patients needed to demonstrate the effect of new therapies. The specific objectives of D-RSC are:
    1. Development of a data sharing platform for Duchenne clinical data
      D-RSC will work with consortium members and other organizations to obtain contributions of clinical data. These data will be converted to a common data structure through the use of Clinical Data Interchange Standards Consortium (CDISC) clinical data standards, and then combined to build a pooled database of de-identified patient data that can include current clinical measures, patient-reported outcomes, pathology, imaging, and other biomarkers that describe the disease progression of Duchenne. D-RSC members will have access to this database per the terms and conditions established for each contributed dataset. The integrated database will be an invaluable research tool for current and future D-RSC projects.
    2. Development and publication of a CDISC therapeutic area standard for Duchenne muscular dystrophy
      During the conversion of data to CDISC standards format to enable pooling of data from multiple sources, C-Path staff will document any gaps in the CDISC clinical data standard as they apply to Duchenne. C-Path will prepare draft supplemental CDISC standards documents and then work with CDISC to publish a new CDISC SDTM therapeutic area standard for Duchenne.
    3. Development of a disease progression model for Duchenne muscular dystrophy via application of the consortium shared data
      This model is envisioned to quantitatively describe disease progression and capture all relevant sources of variability, with three main purposes: 1) serve as the backbone for the future development of a drug-disease-trial model, which can then be turned into a clinical trial simulation platform; 2) serve as a quantitative clinical trial enrichment platform; 3) inform further biomarker efforts.
  • Learn more about this project

Eric Hoffman, Reveragen

  • Funding Type: Xcelerate
  • Amount: $750,000
  • Date: 2/2015 - 2/2016
  • Title: Development of VBP15 for Duchenne Muscular Dystrophy
  • Abstract:This award is to support preclinical activities required for the clinical development of ReveraGen BioPharma's compound, VBP15, a novel steroid derivative designed to reduce side effects while retaining the efficacy of corticosteroids in Duchenne. VBP15 shows loss of activities dependent on GRE-mediated transcription (e.g., activities thought to be responsible for the side effects of corticosteroids), but retention of anti-inflammatory (inhibition of NF-κB) activities (e.g., activities thought to be responsible for the efficacy of corticosteroids in Duchenne). VBP15 also has membrane-stabilizing properties that are superior to prednisolone. In this manner, VBP15 broadens the therapeutic window beyond that achieved by the corticosteroids currently used in Duchenne—potentially preserving the efficacy of these drugs while making them more tolerable to patients. A phase 1 clinical trial of VBP15 in healthy adults is underway. Plans for the Phase 2a/2b program in Duchenne include Newcastle University (Dr. Bushby) and the CINRG group (Dr. Cnaan). This Xcelerate Duchenne Drug Development is providing support for two preclinical toxicology programs (chronic toxicity in two species; juvenile toxicity) that are required by the regulatory authorities and will enable the long-term Phase 2 efficacy studies anticipated to begin in 2015.

The Research Institute at Nationwide Children's Hospital Myology Course

  • Funding Type: Meeting Grant
  • Amount: $30,000
  • Date: 2015
  • Title: 2015 NCH/OSU/Wellstone Myology Course (4th Annual)
  • Details: Meeting dates August 24-28, 2015
  • Meeting Location: Nationwide Children's Hospital and the Ohio State University, Columbus, OH 43205
  • Meeting Goals: The goal of this course is to provide trainees with an up-to-date and expert survey of neuromuscular diseases, and to provide them with practical experience for furthering their clinical or laboratory research career.  The expert faculty addresses clinical syndromes, mechanisms of pathogenesis, molecular therapeutics, and – importantly – aspects of career development. The course is available to both pre-and post-graduate trainees, and both clinical- and laboratory-based trainees are welcome.  We have structured the course so that both groups are together for morning lectures, which emphasize clinical features, molecular pathogenesis, and known and potential therapies.  In the afternoon, clinical trainees receive training in more specifically clinical activities, and laboratory trainees will take part in wet-lab activities, organized by Dr. Denis Guttridge.  At the end of each day, the groups join up again for a keynote lecture, and they gather for a banquet with faculty the evening before the course ends. The Clinical Track is primarily directed at clinical fellows (in Neuromuscular Disease; Genetics; Electrophysiology; Physical Medicine & Rehabilitation; etc.), although other specialties and levels of training are welcome, including medical students, residents in Neurology or Pediatrics, and ancillary staff (e.g., nurse practitioners, or physical therapists). The Laboratory Track is directed primarily toward graduate students and Ph.D. post-doctoral fellows who wish to learn new skills, or expand upon skill sets relevant to their work in their home laboratory.  They choose elective workshops for each afternoon led by NCH/OSU and external faculty.

TREAT-NMD Advisory Committee for Therapeutics(TACT), 11th Meeting, Dublin, Ireland, 27th -29th March 2015

  • Funding Type: Meeting Grant
  • Amount: $14,000
  • Date: 2015
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT) 
  • Meeting Date(s): 27th -29th March 2015
  • Meeting Location: Radisson Blu Royal Hotel Golden Lane, Dublin 8, Ireland
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, andeventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations thatare necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

    Three applications will be reviewed at the upcoming meeting, 2 are concerned with Duchenne Muscular Dystrophy and 1 is concerned with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

    1) NHE-1 inhibitor (PEA-001) for Duchene muscular dystrophy - Stefan Schäfer, Peacock Pharma, Germany

    2) Rimeporide (EMD 87580), a potential disease modifying drug for Duchenne muscular dystrophy - Florence Porte-Thomé, EspeRare Foundation, Switzerland

    3) Gene Therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) using a new orphan drug consisting of an adenoassociated vector carrying the TYMP gene. Phase I/II clinical trial - Ramon Marti, Vall d'Hebron Research Institute (VHIR), Spain

Rachelle Crosbie-Watson, The University of California, Los Angeles

  • Funding Type: Supplement
  • Amount: $157,500
  • Date: 10/2014 – 9/2015
  • Title: Development of Online Course: PS121 “Disease Mechanisms and Therapies
  • Abstract: We have received partial funding from the University of California Office of the President to support development of an on online course at UCLA that is focused entirely on muscular dystrophy. The course will be offered for college credit to undergraduates and graduate students at all campuses across the University of California and beyond (students at other universities will be able to enroll in the course and earn credit toward their college degree).  We have the potential to reach thousands of undergraduates in the STEM majors and teach them about muscle and muscular dystrophy.  It is a unique opportunity to turn students onto the revolution that is occurring in muscular dystrophy at a stage when they are planning their future careers in medicine, research, nursing, and industry. Materials from the course will be adapted for the muscular dystrophy community at large.

Marc Blaustein, Akashi Therapeutics, Inc.

  • Funding Type: GIFTED
  • Amount: $500,000
  • Date: 11/2014 - 12/2015
  • Title: A phase 1b open-label, single and multiple ascending dose study ot evaluate the safety, tolerability and pharmacokinetics of HT-100 in patients with Duchenne muscular dystrophy, and a phase 2a extension study
  • Abstract: This grant supports a Phase Ib/IIa clinical program to evaluate HT-100 (delayed-release halofuginone) in boys with Duchenne muscular dystrophy.  The Phase Ib study is an open-label, single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety, tolerability, PK, and early PD signals of HT-100, a delayed-release, orally-delivered agent in participants with DMD. Study subjects will be enrolled into 5 cohorts of 6 subjects each. Each cohort will undergo dosing in both the SAD and MAD phases of the study. Subjects in each cohort will be dosed in the SAD phase and a Pharmacovigilance Team, based on a comprehensive review of safety and tolerability data, will determine whether dosing can proceed to the MAD phase and the next higher dose level in the SAD phase.

    The Phase 2a Extension study is a 6-month open label extension study that will be offered to all participants who complete the Phase Ib study.  Participants will continue to receive the same dose they received in the MAD phase of the Ib study unless an optimal dose is selected based on the Ib study data and then all participants may be switched to this optimal dose.

Clinical trial travel funds for CAT-1004, Catabasis Pharmaceuticals

  • Funding Type: GIFTED
  • Trial Title: Clinical trial support 
  • Committed: Up to $100,000 

Dongsheng Duan, University of Missouri

  • Funding Type: Exploratory Grant
  • Amount: $55,000
  • Date: 1/2015 – 12/2015
  • Title: Exploring the possibility of SERCA2a therapy in DMD dogs
  • Abstract: A key pathogenic change in Duchenne muscular dystrophy (DMD) is the aberrant elevation of cytosolic calcium.  Supra-physiological calcium triggers proteolysis and muscle death.  Restoration of calcium homeostasis holds promise to treat DMD.  SERCA2a removes cytosolic calcium by its pump function. We recently found AAV SERCA2a gene therapy significantly reduced muscle disease in mdx mice. We now propose this exploratory study to explore if this therapy can be translated to the canine DMD model.  Our study will open the door to a new NIH R01 application to thoroughly evaluate AAV SERCA2a therapy for DMD.

Carrie Miceli, University of California, Los Angeles

  • Funding Type: Exploratory Grant
  • Amount: $50,000
  • Date: 1/2015 – 12/2015
  • Title: Evaluation of exon skipping enhancers for DMD
  • Abstract: DMD is often caused by frame-shifting mutations that abolish dystrophin expression, that can be repaired by AON directed “exon skipping”. Ongoing clinical trials of exon 51 AON demonstrate dystrophin rescue and slowing of disease progression, but skipped dystrophin levels are suboptimal. We identified drugs that boost AON directed exon 51 skipping, which impinge on a common pathway, leading us to predict that second generation drugs may have even greater skip boosting activity. Here we explore their ability to promote skipping alone or in combination with AON directed against exon 51 or other exons currently in the clinical pipeline.

Stan Froehner, University of Washington

  • Funding Type: Bridge Grant
  • Amount: $148,363
  • Date: 1/2015 – 7/2015
  • Title: Functional Analysis of Spectrin-like Repeats in Dystrophin
  • Abstract: Duchenne Muscular Dystrophy (DMD) is caused by mutations in dystrophin, a key protein in muscle signaling pathways. The central region of dystrophin consists of a sequence repeated many times. Many mutations that cause DMD are located in this repeat region. Exon skipping and gene correction therapies require that some of the repeats be removed. We have new evidence that some repeats bind signaling proteins and are not dispensable, as previously thought. In this project, we will determine how the loss of these repeats affects muscle health. This information is needed for rational design of exon skipping and gene replacement therapies.

TREAT-NMD Advisory Committee for Therapeutics (TACT), 10th Meeting, Chicago,USA, 24-26 October 2014

  • Funding Type: Meeting Grant
  • Amount: $7,000
  • Date: 2014
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT) 
  • Details: Meeting Date(s) October 24-26, 2014
  • Meeting Location: InterContinental Chicago Magnificent Mile, Chicago, IL
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases. The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, andeventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations thatare necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and havethe potential to be funded longer term.Three applications will be reviewed at the upcoming meeting, 2 are concerned with Duchenne Muscular Dystrophy and 1 is concerned with Myotubular Myopathy: (1.) Clinical trial of FG-3019 in patients with DMD - Seth Porter, FibroGen Inc, San Francisco, USA (2.) Naproxcinod for the treatment of Duchenne Muscular Dystrophy - Ennio Ongini & Gloria Vigliani, TrophyNOD SAS, Paris, France (3.) A phase 2 single arm, open label, clinical study to evaluate the safety and efficacy of aav8 delivered gene therapy delivered to X-linked  myotubular myopathy (XLMTM)patients ages 8 years and younger - Suyash Prasad, Audentes Therapeutics, Inc, San Francisco, USA

The Research Institute at Nationwide Children's Hospital Myology Course 

  • Funding Type: Meeting Grant
  • Amount: $50,000
  • Date: 2014
  • Title: NCH/Wellstone/OSU Myology Course
  • Details: Meeting Dates August 25-29, 2014
  • Meeting Location: Nationwide Children's Hospital and the Ohio State University, Columbus, OH 43205
  • Meeting Goals: We propose a one-week intensive course directed toward both clinically and laboratory-oriented postdoctoral trainees. Faculty include recognized leaders in neuromuscular care and research, mostly among members of the Nationwide Children's Hospital/OSU Muscle Group. The target audience is international, and we have received requests for enrollment from leading training programs in the United States and abroad.Each morning, attendees will receive lectures on neuromuscular disease genetics and pathophysiology. Each afternoon clinical trainees will receive didactic and hands-on training including but not limited to neuromuscular pathology, methods of clinical assessment, and cardiorespiratory care. Laboratory trainees will have a "wet lab" experience with hands-on training in muscle cell culture, muscle electrophysiology, and muscle precursor cell isolation. Each day will close with the two groups joining for a keynote lecture. The program is designed to provide trainees with an integrated and intensive introduction to principles of neuromuscular disease.

TREAT-NMD Advisory Committee for Therapeutics (TACT), 9th meeting, Berlin, Germany, 9-10 May 2014

  • Funding Type: Meeting Grant
  • Amount: $7,000
  • Date: 2014
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT), 9th meeting, Berlin, Germany, 9-10 May 2014
  • Meeting Date(s): May 9-10, 2014
  • Meeting Location: Berlin, Germany
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations that are necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

    Two applications will be reviewed at the upcoming meeting, one concerned with Duchenne Muscular Dystrophy and one concerned with Spinal Muscular Atrophy

    1. TXA127 for the treatment of muscular dystrophies - Richard Franklin, Tarix Orphan LLC, Cambridge, Massachusetts, USA

    2. Viral vector containing DNA coding for the human SMN protein; for treatment of  5q spinal muscular atrophy’ - Mimoun Azzouz, University of Sheffield, United Kingdom 

    Look at past reviews.

Annemieke Aartsma-Rus, Leiden University Medical Center

  • Funding Type: Exploratory Grant
  • Amount: $100,000
  • Date: 1/2015 - 12/2015
  • Title: Aptamer-based serum biomarker profiling in DMD longitudinal samples
  • Abstract: Evaluation of new therapeutic strategies for Duchenne  has been performed by invasive muscle biopsies. Serum “biomarkers” that correlate with the disease state are less invasive and would allow monitoring over time. However, before these biomarkers can be used in clinical trials, they have to be validated. Here, we aim to validate previously identified serum biomarkers to monitor disease progression and therapeutic response. We will measure these proteins in serum samples derived from DMD patients followed overtime.

Blake Mathie, Talem Technologies, LLC

  • Funding Type: Exploratory
  • Amount: $70,531
  • Date: 5/2015 - 11/2015
  • Title: Methods and metrics for rapid assessment of utility, value, and longevity when deploying new assistive technology to powered wheelchair users. A pilot study using the X-Ar exoskeletal arm support by Talem Technologies
  • Abstract: Recently, Talem Technologies has entered the marketplace with a mobile arm support, the X-Ar. Interest in the X-Ar suggests that this is a viable solution to aid in ADL for the MD community. However, there have been many devices which reach the market and succeed in the early days only to end up quickly forgotten and left in storage. This focus group assessment will explore the intricacies and factors associated with fielding a study to explore the rejection or lasting adoption of assistive technology for the DMD community.

Marc Blaustein, Halo Therapeutics, LLC

  • Funding Type: GIFTED
  • Amount: $100,000
  • Date: 6/2012 - 6/2013
  • Title: A Randomized, Double-blind, Placebo-controlled, Multiple-dose, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of HT-100 in Patients with Duchenne Muscular Dystrophy
  • Abstract: This is a phase II, randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of HT-100 (also known as halofuginone) in Duchenne muscular dystrophy (DMD). As this the first time that the drug will be used in a pediatric population, the study's primary objective is to find a dose regime of HT-100 that is safe and well tolerated in DMD subjects. Secondary objectives include the assessment of the relationship between exposure and effect of HT-100 in several relevant pharmacodynamic endpoints and understanding the pharmacokinetic profile of HT-100 in the pediatric DMD population. Ultimately, this proposal should provide information on the optimal dose/s and inform selection of the primary outcome for the phase III efficacy trial.

Progress Report 7/30/2013:  A phase Ib open-label study of halofuginone is currently enrolling. See more.

TREAT-NMD Advisory Committee for Therapeutics (TACT) 5th Meeting, Arlington VA, USA. 28-29 April 2012

  • Funding Type: Meeting Grant
  • Amount: $24,355
  • Date: 2012
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT) 5th Meeting, Arlington VA, USA. 28-29 April 2012
  • Meeting Date(s): 28th-29th April 2012
  • Meeting Location: Le Meridien Arlington, Virginia
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations that are necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

    DMD Projects Reviewed:
    • Urs Ruegg, PhD, University of Geneva, Geneva. Proposal for clinical investigation of tamoxifen in DMD boys based on results in dystrophic mice
    • Joel Braunstein, MD, FACC, MBA, Tivorsan Pharmaceuticals, USA. Recombinant Biglycan for Treatment of Duchenne and Becker Muscular Dystrophy
    • Paolo Bettica, MD, PhD, Italfarmaco. Italy. A two parts study to assess safety and tolerability, pharmacokinetics, effects on histology and on different clinical parameters of Givinostat in ambulant children with Duchenne Muscular Dystrophy

Urs Ruegg, University of Geneva

  • Funding Type: Investigator Grant
  • Amount: $164,100
  • Date: 5/2012 - 4/2014
  • Title: Preclinical investigation of tamoxifen in mdx miceas prerequisite for a clinical trial in DMD patients
  • Abstract: As part of our search for drugs to treat Duchenne muscular dystrophy, we investigated tamoxifen (TAM) on mdx mice. TAM is used to treat estrogen-dependent breast cancer. TAM fully normalized the motor performance of young and adult mdx mice as well as plasma CK levels. Our findings are extremely encouraging because of TAMs beneficial actions and the absence of undesired effects: It is probably the most powerful substance ever evaluated on dystrophic mice.

Progress report 7/30/2013:  As part of the requirements for funding, some parts of this work are being replicated in an external laboratory.  

Kan Hor, Cincinnati Children’s Hospital

  • Funding Type: Investigator Grant
  • Amount: $84,092.45
  • Date: 6/2012 - 5/2014
  • Title: Early treatment with Aldosterone antagonism attenuates cardiomyopathy in Duchenne MD (Epleronone Trial)
  • Abstract: Historically, most research has focused little on the heart even though it is a major cause of death in DMD patients. This situation is rather astonishing since they possess an absolute genetic risk of heart disease. Remarkably there have been no randomized trials of any cardiac regimen in DMD and no rigorous testing of current cardiac therapy. The purpose of this research is to find out if eplerenone can slow progression of heart dysfunction and scar formation using magnetic resonance imaging.
  • Additional Links:
    Press Release
    ClinicalTrials.gov
    DuchenneConnect

Erik Henricson, University of California, Davis

  • Funding Type: Supplement Grant
  • Amount: $175,000
  • Date: 9/2012 - 8/2014
  • Title: Clinically Meaningful Outcomes for Duchenne Muscular Dystrophy Therapeutic Trials
  • Abstract: The purpose of this grant is to assess novel outcome measures and biomarkers in 100 additional DMD boys in two NIH-funded ancillary studies conducted under the UC Davis/CINRG DMD Natural History Study.

Kristen Vandenborne, University of Florida

  • Funding Type: Supplement Grant
  • Amount: $59,598
  • Date: 9/2012 - 8/2013
  • Title: Magnetic Resonance Imaging as a Biomarker in Muscular Dystrophy – Supplement
  • Abstract: The goal of this project is to study the effect of exon skipping treatment on skeletal muscle in boys with Duchenne muscular dystrophy using magnetic resonance imaging and spectroscopy. Magnetic resonance is a completely noninvasive technique that allows for the assessment of muscle quality and may be well suited for inclusion in clinical trials. We anticipate that the results of this study will be valueable to future clinical trials.

Dean Burkin, University of Nevada, Reno

  • Funding Type: Supplement Grant
  • Amount: $25,000
  • Date: 10/2012 - 9/2014
  • Title: Laminin-111 protein therapy for Duchenne Muscular Dystrophy
  • Abstract: Duchenne Muscular Dystrophy (DMD) is a devastating neuromuscular disease for which there is currently no effective treatment or cure. We have recently shown that laminin-111 protein therapy can prevent muscle disease in the mdx mouse model of Duchenne muscular dystrophy. At the time of diagnosis, Duchenne patients have already developed significant muscle disease and it is unclear if laminin-111 protein therapy is effective at preventing disease progression after it has already started. To translate the above exciting result into a therapy for Duchenne patients, we will determine if laminin-111 protein therapy can prevent muscle pathology after disease onset in mouse and GRMD dog models of Duchenne muscular dystrophy. Results from this study will pave the way for developing laminin-111 as a highly potent, novel therapeutic for DMD.

Donsheng Duan, University of Missouri

  • Funding Type: Investigator Grant
  • Amount: $280,425.60
  • Date: 9/2012 - 8/2014
  • Title: SERCA2a gene therapy for Duchenne cardiomyopathy
  • Abstract: Duchenne muscular dystrophy (DMD) patients often suffer from heart disease. Gene therapy holds promise to treat DMD. However, current gene therapy strategies cannot fully meet the need of the heart. AAV SERCA2a mitigates heart failure in humans. We found AAV SERCA2a ameliorated ECG defects in mdx mice. Here we will determine whether AAV SERCA2a alone or in combination with AAV micro-dystrophin can treat DMD heart disease. Our finding will significantly advance DMD heart disease therapy.

Stanley Nelson, University of California, Los Angeles

  • Funding Type: Investigator Grant
  • Amount: $100,029
  • Date: 11/2012 - 10/2013
  • Title: Pilot Project to identify genetic modifiers of Duchenne muscular dystrophy
  • Abstract: Mutations in the DMD gene cause Duchenne muscular dystrophy. While the mean age at which DMD boys lose ambulation is 10 years, there is a large variation. This variability may be due to DNA differences in unknown genes in which rare variants or other mutations are changing protein function. To find these genes, we will sequence all genes in males with DMD having unusually severe or unusually mild skeletal muscle progression using whole exome sequencing, and compare to 7,000 control individuals.

Toshifumi Yokota, University of Alberta

  • Funding Type: Exploratory Grant
  • Amount: $50,000
  • Date: 9/2012 - 8/2013
  • Title: Exons 45-55 skipping with a cocktail antisense oligo
  • Abstract: A most promising therapeutic approach to treat DMD is exon skipping therapy. Previously we demonstrated the first bodywide rescue with exon skipping in mouse and dog models of DMD. However, exon skipping faces two major hurdles; limited applicability, and uncertain function of the resulting short protein (dystrophin). In theory, exon 45-55 multiple exon skipping could rescue over 60% of patients with deletion mutations, while deletions of this region are associated with asymptomatic or exceptionally mild symptoms. In this proposal, we aim to rescue dystrophin expression with exons 45-55 multiple skipping in DMD model mice.

NCH/Wellstone/OSU Myology Course, Columbus, OH. 10-14 September 2012

  • Funding Type: Meeting Grant
  • Amount: $25,440
  • Year: 2012
  • Title: NCH/Wellstone/OSU Myology Course
  • Meeting Date(s): 10-14 September 2012
  • Meeting Location: Nationwide Children's Hospital and Ohio State University, Columbus, Ohio
  • Meeting Goals: We propose a one-week intensive course directed toward both clinically and laboratory-oriented post-doctoral trainees. Faculty include recognized leaders in neuromuscular care and research, mostly among members of the Nationwide Children's Hospital/OSU Muscle Group. The target audience is international and we have received requests for enrollment from leading training programs in the United States and South America.

    Each morning, attendees will receive lectures on neuromuscular disease genetics and pathophysiology. Each afternoon clinical trainees will receive didactic and hands-on training including but not limited to neuromuscular pathology, methods of clinical assessment, and cardiorespiratory care. Laboratory trainees will have a "wet lab" experience with hands-on training in muscle cell culture, muscle electrophysiology, and muscle precursor cell isolation. Each day will close with the two groups joining for a keynote lecture.

    The program is designed to provide trainees with an integrated and intensive introduction to principles of neuromuscular disease.

Volker Straub, University of Newcastle Upon Tyne

  • Funding Type: Exploratory Grant
  • Amount: $49,003.20
  • Date: 9/2012 - 8/2013
  • Title: Development of MEMRI as an outcome measure for pre-clinical studies in the mdx mouse
  • Abstract: Many therapies are emerging to treat muscular dystrophy, including viral gene therapy and exon skipping. One problem which is limiting the refinement of these therapies is a lack of non-invasive methods to measure their effectiveness. We are developing a novel technique based on MRI scanning which is capable of detecting calcium levels in the muscle cell. Since calcium is universally increased in dystrophic muscle, this provides a direct, non-invasive measure of the ongoing pathology in muscle tissue in real time. As a tool, this may be extremely useful in refining existing therapies, speeding their transition to the clinic.

TREAT-NMD Advisory Committee for Therapeutics (TACT). 6th Meeting, Prague, Czech Republic. 27th-28th October 2012

  • Funding Type: Meeting Grant
  • Amount: $24,186.50
  • Year: 2012
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT)
  • Details: Meeting Date(s) 27-28 October 2012
  • Meeting Location: Prague, Czech Republic
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations that are necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

    Four applications will be reviewed at the upcoming meeting, all of which are concerned with Duchenne Muscular Dystrophy.

    1. P2X7 purinoceptor as a target for pharmacotherapy of Duchenne Muscular Dystrophy. Dariusz C Gorecki MD, PhD (Professor of Molecular Medicine). University of Portsmouth.
    2. VBP15 for the treatment of DMD. Erica Reeves. PhD. (Vice President, Research & Operations). ReveraGen BioPharma, Inc.
    3. CAT-1004, a novel anti-inflammatory agent for treatment of Duchenne Muscular Dystrophy. Joanne M. Donovan, MD, PhD. (Chief Medical Officer). Catabasis Pharmaceuticals, Inc.
    4. Novel myostatin antagonist peptides to enhance muscle function. Patricio Sepulveda. (COO and Program Director). Myostin Therapeutics Pty Ltd.

Robert Griggs, University of Rochester

  • Funding Type: Supplement Grant
  • Amount: $78,356.80
  • Date: 1/2014 - 1/2016
  • Title: Predicting the benefit vs the side effects of corticosteroids in Duchenne muscular dystrophy
  • Abstract: This grant requests support for studies ancillary to the NIH-funded (2010-2016) clinical trial: Finding the Optimum Regimen of Corticosteroids for Duchenne Muscular Dystrophy (FOR DMD). This study (which commences in the Fall, 2012) will enroll 300 boys with Duchenne muscular dystrophy (DMD) from 40 sites in 5 countries. Boys will be randomized to one of the 3 regimens in widest use: daily prednisone (0.75 mg/kg/d); daily deflazacort (0.9 mg/kg/d); intermittant prednisone (0.75 mg/kg/d 10 days on/10 days off). Boys will be followed for 3-5 years and receive standardized preventive measures for side effects of steroids and for complications of DMD. The study’s outcome measure is a combined measure of strength and satisfaction with the treatment regimen. Ancillary studies of genetic and biochemical markers will seek to determine factors predicting disease severity, disease complications and favorable and unfavorable responses to steroids.
  • Suspended due to milestone delay

Kanneboyina Nagaraju, Children’s Research Institute

  • Funding Type: Exploratory Grant
  • Amount: $50,000
  • Date: 9/2012 - 8/2013
  • Title: Long-term efficacy and side effect profile of compound A, a selective glucocorticoid receptor modulator in mdx mice
  • Abstract: Glucocorticoids (GCs) are currently the only proven therapy in Duchenne Muscular Dystrophy (DMD) but the benefits of chronic therapy are associated with substantial side effects. Compound A (CpdA) is a drug that possesses the anti-inflammatory property of GCs but lacks adverse effects. It achieves this by acting on the Glucocrticoid Receptor (GR) in a way that does not involve mechanisms associated with these side effects. We have shown that CpdA improves pathology and reduces inflammation in mdx mice. We aim to confirm that efficacy in chronic CpdA treatment is associated with reduced or absent metabolic, growth, and bone effects.


*Note: Studies were halted due to toxicity

Federica Montanaro, Ph.D.

  • Funding Type: Supplement Research Grant 
  • Amount: $52,500 
  • Date: 2/2012 - 1/2013 
  • Title: Analysis of protein interactions mediated by micro-dystrophin in the mdx heart Research Grant 
  • Abstract: Current micro-dystrophin gene therapy does not fully protect from cardiac disease in DMD. We have identified two new proteins that interact with dystrophin in the heart and control cardiac contraction. We have found that their binding to micro-dystrophin is affected. The main goal of the proposed project is to understand how impaired binding to micro-dystrophin affects cardiac contraction.

Joel Braunstein, Tivorsan Pharmaceuticals

  • Funding Type: GIFTED Corporate Grant
  • Amount: $556,000
  • Date: 6/2012 - 6/2014
  • Title: Recombinant Biglycan for Treatment of Duchenne and Becker Muscular Dystrophy
  • Abstract: Tivorsan Pharmaceuticals seeks to develop and commercialize a recombinant, humanized form of biglycan (rhBGN) suitable for all genetic forms of DMD. Tivorsan’s approach to treat DMD is by recruiting utrophin to the muscle cell membrane. Utrophin is a protein that is able to replace dystrophin function. Biglycan represents a compelling candidate for chronic DMD treatment for several reasons: (i) As a homolog of a natural human protein expressed in developing muscle, rhBGN is expected to be safe, well tolerated and carry low risk for immunogenicity in humans; (ii) Since biglycan binds striated muscle-specific sarcoglycans, rhBGN could have preferential/selective activity for the muscles impacted in DMD; (iii) As reported recently in the Proceedings of the National Academy of Science, rhBGN works through a unique mechanism of action and is effective when administered systemically-administered. In dystrophin-deficient (mdx) mice, rhBGN increased utrophin expression at muscle cell membranes with a corresponding improvement in muscle structure and function.

Progress Report 7/30/2013:  This is a milestone-driven project.  To date the project has met its first two milestones as determined by an independent scientific steering committee and has received payments of $390,000.  The third milestone is due in September of 2013 and the last in December of 2013.

Katherine Mathews, M.D.

  • Funding Type: Exploratory Grant
  • Amount: $33,337.50
  • Date: 11/2011 - 4/2012
  • Title: Therapeutic application of selective glucocorticoid receptor modulators in Duchenne muscular dystrophy - balancing efficacy with an improved side-effect profile
  • Abstract: Recent studies suggest that there is an increased rate of Autism Spectrum Disorders (ASD) and Obsessive-Compulsive Disorder (OCD) in childhood onset Duchenne Becker Muscular Dystrophy (DBMD). Studies show that early intervention can improve the long-term problems associated with ASD and OCD. We propose to assess the rate of ASD and OCD in the DBMD population in Iowa. We will report the rates by age, disease status, and cognitive skills and compare to the general population rates. Improved knowledge of the rates will guide clinicians in appropriate screening and intervention and result in improved quality of life for patients and families.

Jon Tinsley, Ph.D., Summit plc.

  • Funding Type: GIFTED
  • Amount: $250,000
  • Date: 6/2011 - 10/2011
  • Title: Clinical Development of SMTC1100, a Utrophin Upregulator for Duchenne Muscular Dystrophy
  • Abstract: Summit plc have taken an alternative pharmacological approach to DMD developing a strategy which should be appropriate to treat all patients irrespective of their dystrophin mutation and would also have the potential to target skeletal and cardiac muscle. We have been developing novel small molecules which can transcriptionally upregulate the utrophin gene.  The demonstration that increased utrophin can prevent the muscular dystrophy in the mdx mouse has been confirmed by others. SMT C1100 was the final product of an exhaustive chemical screening and optimisation campaign. In the recent Phase I clinical trial sponsored by BioMarin, SMT C1100 (BMN195) achieved plasma exposure marginally below the predicted efficacy levels and was deemed safe with no reported aserious adverse events.  This is frequently a problem in Phase I trials however low compound exposure levels can often be circumvented using new formulations of the drug to increase bioavailability. Summit is proposing to fast track assessment of a second readily available formulation of SMT C1100 in a new Phase I healthy volunteer clinical trial.  It is our belief that this approach will give SMT C1100 the best opportunity of being able to demonstrate its true potential as a viable DMD therapy.

Progress Report 7/30/2013:  The GIFTED grant of $250,000 enabled Summit to start the manufacture of clinical grade SMT C1100 prior to the completion of a larger funding round, which may enable the start of Phase I clinical trials sooner than anticipated.  The project recently underwent a review by the TREAT-NMD TACT committee—the public summary of that report can be accessed here(TACT reviews are funded, in part, by PPMD).

Tony Huynh, M.B.B.S., F.R.A.C.P

  • Funding Type: Weisman Fellowship
  • Amount: $100,000
  • Date: 5/2011 - 5/2013
  • Title: Therapeutic application of selective glucocorticoid receptor modulators in Duchenne muscular dystrophy - balancing efficacy with an improved side-effect profile
  • Abstract: Glucocorticoids (steroids) remain the only drug treatment clinically recognised to improve muscle function in DMD. Their use is, however, often limited by significant side effects such as weight gain, bone weakness, impaired growth, and unfavorable changes in metabolism. Compound A is a natural compound which possesses the positive effects of steroids in reducing inflammation without the side effects. This project aims to assess whether Compound A will reduce muscle damage without the side effects in a mouse model for DMD.

Tejvir Khurana, M.D., Ph.D.

  • Funding Type: End Duchenne Grant
  • Amount: $97,869
  • Date: 8/2011 - 7/2013
  • Title: Validation & Preclinical studies on Drugs discovered by Utrophin promoter HTS for DMD therapy
  • Abstract: Utrophin (dystrophin related protein) is closely related to dystrophin, the gene mutated in Duchenne's Muscular Dystrophy (DMD). When over-expressed utrophin substitutes for the missing dystrophin and hence a promising therapeutic strategy for DMD. Using High Throughput Screening we have identified 14 drugs that upregulate the utrophin gene promoter. Here we will a) validate the drugs we have obtained and b) treat mdx mice with the drugs we have identified to help harness its therapeutic potential for DMD patients.
  • Press Release.

Jerry Mendell, M.D., Ph.D., Cincinnati Children’s Hospital

  • Funding Type: Investigator Grant
  • Amount: $600,000
  • Date: 6/2010 -  5/2013
  • Title: Follistatin gene therapy to improve quadriceps muscle strength
  • Abstract: Viral-mediated gene transfer of the follistatin gene to increase muscle strength emerges as a sound therapeutic strategy based on our published, peer reviewed, proof of principle studies (to be reviewed in this proposal and reprints attached)1,2 in mouse and non-human primate. The quadriceps muscle emerges as the target site for this approach because of need and clinical practicality. These important concepts further merge into a therapeutic plan for two diseases with debilitating quadriceps muscle weakness that will lead to clinically meaningful benefit by increasing the strength of the knee extensor muscles. Aim 1. Prepare rAAV1.CMV.follistatin344 vector for clinical trial to improve quadriceps muscle strength in sporadic inclusion body myositis patients.  Aim 2. Conduct a 6 month clinical trial of intramuscular rAAV1.CMV.follistatin344 to quadriceps muscles in sporadic IBM and Becker muscular dystrophy patients.
  • Deliverables:
    • Manufacture of vector of sufficient quantity and quality to complete the clinical study (Complete)
    • IND approval (Complete)
    • Inject first IBM patient (Complete)
    • Complete low dose sIBM participants (Complete)
    • Complete low dose BMD participants (Complete)
    • Low dose data is reviewed with oversight committee and is found not to prevent the high dose study (Complete)
    • Complete high dose sIBM participants
    • Complete high dose BMD participants
    • Report results to oversight committee
  • Participants: For clinical trial information, please visit ClinicalTrials.gov

Paul Janssen, M.L., Ph.D.

  • Funding Type: Exploratory Grant
  • Amount: $50,000
  • Date: 8/2011 - 1/2012
  • Title: Prevention of eccentric stress damage and contractile dysfunction by glycoprotein-based membrane strengthening in cardiac muscle.
  • Abstract: We have recently made observations that enhanced membrane protein glycosylation has a profound effect in preventing contraction-induced injury of skeletal muscle in a mouse model of DMD. In order to treat DMD effectively, ultimately not only limb skeletal muscle, but also diaphragm muscle and heart muscle must be treated. Here we aim to achieve enhanced membrane “stickiness” in the heart, and assess its functional effectiveness in preventing contraction-induced injury. Together with skeletal muscle function enhancement, this research may open up new avenues of effective therapeutic strategies.

Jill Rafael-Fortney, Ph.D.

  • Funding Type: Bridge Grant
  • Amount: $50,000
  • Date: 8/2011 - 1/2012
  • Title: Optimization of renin-angiotensin-aldosterone inhibitors as a treatment for dystrophin-deficient skeletal muscles and heart. - 2011
  • Abstract: We have recently observed a profound improvement in a mouse model of Duchenne muscular dystrophy resulting from treatment with the FDA approved drugs lisinopril and spironolactone. Muscle strength in skeletal muscles in limbs and those used in respiration was doubled in treated mice compared to untreated mice and function of the heart was also significantly improved. Ongoing muscle damage in skeletal muscles and heart was almost completely prevented. This project aims to define the parameters required for optimal treatment of dystrophic mice. These studies have direct implications for designing clinical trials for the DMD patient population.
  • Press Release.

Federica Montanaro, Ph.D.

  • Funding Type: Bridge Grant
  • Amount: $50,000
  • Date: 8/2011 - 1/2012
  • Title: Analysis of protein interactions mediated by micro-dystrophin in the mdx heart Bridge Grant
  • Abstract: Micro-dystrophin gene therapy is currently in clinical trial for skeletal muscle treatment of Duchenne Muscular Dystrophy (DMD) patients. Micro-dystrophin can be delivered to the heart however current designs are not optimized to fully protect from cardiac disease. The proposed project is aimed at revealing differences in protein binding between dystrophin and micro-dystrophin in the heart. This information will then be used to optimize the design of micro-dystrophin to improve cardiac protection. It will also identify new proteins involved in heart disease in DMD that could be potential targets for drug treatment.

Stan Froehner, Ph.D.

  • Funding Type: Investigator Grant
  • Amount: $132,322
  • Date: 11/2011 - 11/2013
  • Title: Combinatorial Use of Sildenafil and Prednisone to Treat Dystrophin-Deficient Cardiac and Skeletal Muscle
  • Abstract: Drugs that slow the progression of skeletal muscle degeneration and heart disease will improve quality of life, extend longevity and allow genetic correction at later stages of the disease. Our studies of Viagra, an FDA drug that amplifies the nNOS signaling pathway, demonstrate a marked improvement in heart and diaphragm function in the mdx mouse. In preparation for a clinical trial on young DMD boys, we will determine if sildenafil and prednisone can be used in combination.
  • Deliverables:
    • 30 mdx mice on drug(s)
    • All mice on drugs
    • 1st echos completed
    • Skeletal muscle physiology completed
    • Skeletal muscle tissue analysis completed (histology, western blots for fibrosis, etc) 2nd echos completed
    • 3rd echos completed
    • Muscle studies on long term treated mice completed
    • Data analyses completed and compiled for publication
  • Timeline
    • November 2011: Launch
    • November 2012: Progress Report Year 1

Somalogic, Inc and Cincinatti Children’s Hospital Medical Center

  • Funding Type: Contract
  • Amount: Up to $40,900
  • Date: 4/2011 - 3/2012
  • Title: The identification of biomarkers in Duchenne muscular dystrophy via aptamer-based microarray technology
  • Details: PPMD has entered a three way agreement with biotechnology company Somalogic Inc. and Cincinnati Children’s Hospital Medical Center (CCHMC) to use Somalogic’s proprietary screening technology to identify biomarkers for Duchenne muscular dystrophy.“Biomarkers” are proteins or other molecules in the body that can be measured to provide information about disease state or disease progression. They can be used in diagnostics or to determine if an experimental therapy is having an effect on the condition it’s being used to treat. A biomarker that is known to reliably provide this type of information can accelerate the time it takes to conduct a clinical study and approve new drugs. Biomarkers may also lead to the identification of new therapeutic targets.
  • Press Release: Parent Project Muscular Dystrophy Awards Over $40,000 Grant to SomaLogic Study (PDF)
  • Recruitment Information: Coming Soon

Dongsheng Duan, Ph.D., University of Missouri

  • Funding Type: PPMD Investigator Award
  • Amount: $116,069  
  • Year: 2010 - 2011
  • Title: Identify novel AAV vectors for canine heart transduction by peripheral vein injection
  • Abstract: Duchenne cardiomyopathy is one of the two leading causes of morbidity and mortality in Duchenne muscular dystrophy (DMD). Unfortunately, there is no ongoing NIH sponsored research to develop Duchenne cardiomyopathy gene therapy. As a matter of fact, a search of the 1972-2009 NIH grant database fails to pull out any grant on Duchenne cardiomyopathy gene therapy. To address this unmet need, here we propose to develop adeno-associated virus (AAV) mediated Duchenne cardiomyopathy gene therapy in a canine model. Systemic gene delivery has been considered as the most likely approach to lead to whole body correction in DMD. Despite the success of robust systemic AAV gene transfer in rodents, only one study (from our group) has evaluated AAV-9 gene transfer in dogs. We achieved whole body skeletal muscle transduction. However, we found nominal expression in the heart. Developing an AAV vector that can efficiently infect the dog heart is fundamental to Duchenne cardiomyopathy AAV gene therapy.
  • Publications:
    • Duan, D. Research and Reports in Biology 2011 Mar;2011(2):31-42. Duchenne muscular dystrophy gene therapy: Lost in translation?
    • Fine et al. Neuromuscular Disorders 2011 Jul; 21(7):453-61. Age-matched comparison reveals early electrocardiography and echocardiography changes in dystrophin-deficient dogs.
    • Shin et al. Human Gene Therapy 2012 Mar;23(3):287-94. Humoral immunity to AAV-6, 8 and 9 in normal and dystrophic dogs.
    • Shin et al. Methods in Molecular Biology 2012; 798:267-84. Recombinant adeno-associated viral vector production and purification.
    • Wasala et al. Journal of Gene Medicine 2011 Oct; 13(10):557-65. The evolution of heart gene delivery vectors.
    • Yue et al. Methods in Molecular Biology 2011; 709:313-29. Whole Body Skeletal Muscle Transduction in Neonatal Dogs with AAV-9.

H. Lee Sweeney, Ph.D., University of Pennsylvania

  • Funding Type: PPMD Investigator Award
  • Amount: $300,000
  • Year: 2009
  • Title: Combined Therapeutics as a Treatment for DMD

Meg Sleeper, University of Pennsylvania

  • Funding Type: PPMD Investigator Award
  • Amount: $100,000
  • Year: 2009
  • Title: Large animal model/studies Therapeutics in DMD

Accleron ACE-031 Clinical Trial 

  • Funding Type: Gifted: Faster (ACT Now)
  • Trial Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACE-031 (ActRIIB-IgG1) in Subjects With Duchenne Muscular Dystrophy
  • Committed: Up to $100,000 from 2010 to the end of 2011; $5,000/site.
  • Awarded to date:
    • (2010) Alberta Children’s Hospital, Calgary, Alberta, Dr. Jean Mah
    • (2010) Lawson Health Research Institute, London, Ontario, Dr. Craig Dr. Campbell
    • (2010) BC Children’s Hospital, Vancouver, British Columbia, Dr. Kathy Katherin Selby
    • (2010) McMaster University Medical Center, Hamilton, Ontario, Dr. Mark Mark Tarnopolsky
  • Learn more about ACE-031 in the Therapeutic Pipeline

AVI-4658 (Antisense oligonucleotide to skip exon 51) Clinical Trial

  • Funding Type: Gifted: Faster (ACT Now)
  • Trial Title: Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Dose, Dose-Escalation Safety, Tolerability, Efficacy, and Pharmacokinetic Study of AVI-4658, a Phosphorodiamidate Morpholino Oligomer, Administered Over 12 Weeks in the Treatment of Ambulant Subjects with Duchenne Muscular Dystrophy
  • Committed: Up to $50K
  • (2011) Nationwide Children’s Research Institute, Columbus, Ohio, Dr. Jerry Mendell
  • Learn more about AVI-4658 in the Therapeutic Pipeline

Nicholas Whitehead, University of Washington

  • Funding Type: Weisman Fellowship
  • Year: 2009
  • Title: The Effects of Sildenafil on mdx Skeletal Muscle
  • Amount: $50,000

Nicholas Dobes, University of North Carolina

  • Funding Type: Weisman Fellowship
  • Year: 2010
  • Title: A New Technology to Isolate Muscle Stem cells for Muscular Dystrophy Research and Treatment
  • Amount: $50,000
  • Abstract: Since being discovered in 1989, the use of muscle precursor cells (muscle stem cells) from a normal donor to restore dystrophin expression within dystrophic host muscles has brought an abundance of possibilities to regenerative medicine. Due to the potential of rejection of outside cells, the use of the host’s cells has proven more effective. These stem cells have the potential to regenerate skeletal muscle and are highly applicable to patients with muscular dystrophy, a genetic disorder that is responsible for the weakening and death of muscle cells and tissues. In order to use these stem cells for research or therapy, processes such as screening for intracellular markers must first be used for stem cell determination. Drawbacks to current methods of stem cell screening by intracellular markers include the required destruction of the cell, thus rendering it useless for future applications. The goal of this project is to utilize a newly developed cell-based array technology to circumvent this problem. Large segregated arrays will allow cells to be cultured on individual pallets and expanded across bridges to adjacent pallets. These colonies will then be divided in half producing portions used for stem cell determination via destructive staining procedures and portions retained for further culture. The research aims are as follows:
    1. Optimize culture conditions for myoblasts on micropallet arrays.
    2. Develop and optimize protocol for subdividing colonies, generating colonies for destructive analysis, and future culture.
    3. Demonstrate that Pax7+ colonies identified on the array can be collected and expanded in culture.

Melissa Spencer, UCLA

  • Funding Type: End Duchenne GAP
  • Amount: $50,000
  • Year: 2009-2010
  • Title: Osteopontin as a therapeutic target in DMD (anti-fibrotic)
  • Abstract: Aim 1) To test the hypothesis that the reductions in fibrosis observed in OPN/mdx diaphragms also translate to improved pulmonary function. Aim 2) To test the hypothesis that the reductions in fibrosis observed in OPN/mdx hearts also translate to improved cardiac function. Aim 3) To validate that the inflammatory changes that were observed body-wide in OPN/mdx mice are also occurring in the diaphragm muscle specifically.

Carmen Bertoni, UCLA

  • Funding Type: End Duchenne GAP
  • Amount: $75,000
  • Year: 2009-2010
  • Title: Improving the efficiency of antisense oligonucleotides (exon skipping)
  • Abstract: Oligonucleotides-mediated gene correction. The studies proposed in the application will permit us to identify compounds capable of increasing the repair efficiency of ssODNs independently from the type of mutation targeted for repair. Since the last review we have further refined and optimized an HTS screen capable of identifying modulator of gene correction using ssODNs. Funding from PPMD will be used to screen the library containing all the drugs approved by FDA. These studies will enable us to verify the efficiency of the screening protocol and might allow us to develop a safe approach to DMD using ssODNs. In addition to promoting gene correction strategies for muscular dystrophy, these studies will help us generate the data necessary to strengthen the application submitted to NIH. The research proposed in this application will be conducted within the 12 months allowed by PPMD and will be divided into two major aims.

Krista Vandenborne, University of Florida

  • Funding Type: Supplement Grant
  • Amount: $17,050
  • Year: 7/2013 – 6/2014
  • Title: Magnetic Resonance Imaging as a Biomarker in Muscular Dystrophy - Supplement 2013
  • Abstract: The objective of this supplemental study is to identify potential urine and blood biomarkers in Duchenne muscular dystrophy and correlate them with assessments of disease severity and progression that are being obtained as part of the ongoing ImagingDMD study.  Samples will be shared with two industry collaborators.

Bradley Hodges, Prothelia

  • Funding Type: End Duchenne GAP
  • Amount: $46,000
  • Title: Lam III, Integrin as a potential therapy for DMD
  • Abstract: Our objective is to develop an intravenously delivered protein therapy for treatment of Duchenne muscular dystrophy (DMD), a disease that occurs in 1 of every 3,500 male births. DMD is caused by a deficiency of dystrophin, a cytoskeletal protein which tethers the contractile apparatus to the membrane and basal lamina of skeletal and cardiac muscles and protects myofibers from the shear forces of muscle contraction. There are no approved therapies for DMD and the only available treatments are the steroids prednisone or deflazacort. Approaches for treatment of DMD include dystrophin mRNA rescue technologies such PTC124 and exon skipping, and dystrophin replacement through gene and stem cell therapy. Other approaches under consideration employ intravenous proteins or small molecule therapies that upregulate the expression of nondystrophin surrogates such as utrophin or the alpha7 integrin.

Justin Fallon, Brown University

  • Funding Type: End Duchenne GAP
  • Amount: $264,000
  • Year: 2008-2009
  • Abstract: This U01 Translational Research in Muscular Dystrophy will support the development of recombinant human biglycan (rhBGN) as a therapy for Duchenne Muscular Dystrophy. It builds upon work carried out by the Fallon laboratory over the past 20 years on the role of extracellular matrix proteins in organizing the muscle cell surface, including recent studies showing that systemically-delivered rhBGN upregulates utrophin at the sarcolemma, counters the dystrophic phenotype in mdx mice, and improves muscle function. In our preliminary work we have found that rhBGN is effective when delivered at 3 week intervals and at doses of <10mg/kg. Moreover, because rhBGN is an endogenous protein normally expressed at high levels during development, rhBGN is expected to be hypoimmunogenic. We propose a 5-year development plan to optimize rhBGN so that it meets purity and quality criteria for use in humans. This plan includes pilot studies to optimize the protein structure, PK and biodistribution studies in rodents and non-human primates, and dose optimization in mdx mice with well characterized material produced from a stable cell line under GLP conditions. To maximize the efficiency, accuracy, and speed of this process, the work will make use of standardized models and assays as well as collaborations with several vendors expert in biologies development. We will work with the Wellstone core facility at U. Pennsylvania to perform muscle physiology measurements. We have also enlisted consultants with extensive expertise in the manufacturing, testing, and regulatory issues that are unique to biologies. Two clinicians with experience leading DMD trials will also serve as consultants; their advice and input will be integrated in all stages of this development process.

Duchenne Connect

  • Funding Type: GIFTED: Faster (Infrastructure Project)
  • Amount: $175,000/year
  • DuchenneConnect serves as a central hub linking the resources and needs of those living with Duchenne/Becker muscular dystrophy and the professional community, including clinicians, policymakers, industry professionals, and medical researchers. We offer registered members resources to assist with early, appropriate, and least invasive diagnosis, care, and management; better understand the benefits and limitations of genetic testing; and assist in understanding and development of new treatment trials.  
  • DuchenneConnect.org

6 Minute Primary Outcome Measure in DMD

  • Funding Type: GIFTED: Faster (Infrastructure Project)
  • PTC Therapeutics
  • Amount: $100,000
  • Data published in the December 2010 issue of the medical journal Muscle and Nerve confirm the utility of six-minute walk distance (6MWD) as a clinically meaningful endpoint in dystrophinopathy, a disease continuum comprising Duchenne and Becker muscular dystrophy (DBMD). The data showed that boys with DBMD experience a significant decline in walking ability compared to healthy boys over one year, suggesting that slowing the loss of walking ability is a major treatment goal. The observational study, which provides the first longitudinal natural history data reflecting changes in 6MWD in patients with DBMD, was conducted at the University of California-Davis, sponsored by PTC Therapeutics and funded in part by a grant from Parent Project Muscular Dystrophy (PPMD).
  • Publication: McDonald et al. Muscle Nerve 2010 Ar; 41(4):500-10. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. 

Outcome Measures for Non-ambulatory Patients

FASEB Muscle Stem Cell Meeting

  • Funding Type: Meeting Support
  • Grantee: Dr. Thomas Rando, Stanford University

PPMD Annual Connect Conference

  • Funding Type: Meeting Support
  • Grantee: PPMD Meeting

Western Australia NMD meeting

  • Funding Type: Meeting Support
  • Grantee: Dr. Steve Wilton, University of Western Australia, Perth

Endocrinology in Duchenne

  • Funding Type: Meeting Support
  • Grantee: PPMD Meeting

Exon-skipping AON meeting

  • Funding Type: Meeting Support
  • Grantee: Dr. Edward Connor, Childrens National Medical Center

TREAT-NMD Advisory Committee for Therapeutics (TACT), 4th Meeting, Lisbon, Portugal 15th-16th October 2011

  • Funding Type: Meeting Grant
  • Amount: Up to $25,000
  • Year: 2011
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT), 4th Meeting, Lisbon, Portugal 15th-16th October 2011.
  • Details: Meeting Date(s) 15th - 16th October 2011
  • Meeting Location: Hotel Santa Marta, S.A. Rua Santa Marta, 48 / 1150-297, Lisbon, Portugal.
  • Meeting Goals:
    To provide the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases. Three applications will be reviewed at the Lisbon meeting.

    The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations.

    The TACT review and detailed report with recommendations are confidential and provided directly to the investigator within 6 weeks of the meeting.

    PPMD support (50% of the meeting costs) is kindly requested for the review of applications 1 and 2 which relate to DMD/BMD.
  • DMD Projects Reviewed:
    • “A 6-month multicenter, randomised, double-blind, placebo-controlled, Phase IIa proof of principle study of naproxcinod (HCT 3012) 750 mg bid in patients with Becker Muscular Dystrophy (BMD)” NicOx SA. REVIEW AVAILABLE SOON
    • “A randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of HT-100 in patients with Duchenne muscular dystrophy” Halo Therapeutics, LLC. REVIEW AVAILABLE SOON.

2nd Annual Clinical Outcome Measures in DMD Workshop 2011

  • Funding Type: Meeting Grant
  • Amount: $1,300
  • Year: 2011
  • Title: 2nd Annual Clinical Outcome Measures in DMD Workshop 2011
  • Details: Meeting Date(s) 10th - 11th July 2011
  • Meeting Location: Baltimore Waterfront Marriott
  • Meeting Goals: The goal of this meeting is to continue to bring together global thought leaders and researchers in outcome measures and clinical trial design to further our understanding of the current natural history of DMD and how this impacts choice of endpoints for clinical trial design. The group met last year and a publication is due out shortly that summarizes the main findings of that meeting. The sheer power of the number of patients that were presented at the first meeting and have been followed longitudinally combined with the consistency of results between data sets, was substantial. The effect of steroids on the natural history of the disease was looked as well. This year’s meeting will build on the collaboration that was established last year and further discuss and evaluate some of the issues that face those who are planning trials in DMD. Also, smaller patient groups such as the non-ambulant and the very young will be discussed. As there are many therapies now entering clinical trials, this information is very relevant. The meeting also serves to bridge the gap between industry and research as there will be a panel discussion where industry will have the opportunity to identify the challenges they face and how this group could most help them.

TREAT-NMD Advisory Committee for Therapeutics (TACT) 3rd Review Meeting 2011

  • Funding Type: Meeting Grant
  • Amount: $24,577
  • Year: 2011
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT) 3rd Review Meeting - 2011
  • Details: Meeting Date(s) 15th-16th January 2011
  • Meeting Location: Ritz-Carlton Hotel Charlotte, North Carolina 28202
  • Meeting Goals:
    To discuss and formulate feedback and advice on applications submitted to TACT.

    PPMD support is requested for application 1 (i.e. 50% of meeting costs) which relates to DMD.

    The advice will be given in the form of a written report to the applicants within 6 weeks of the meeting.

    TACT's goal is to position the potential therapy along a realistic pathway to eventual clinical trial and registration by evaluating preclinical data as well as drug development considerations that are crucial for the conduct of studies that generate meaningful data. In close collaboration with the TREAT-NMD clinical trials coordination centre (Freiburg, Germany), TACT is also dedicated to providing information on optimal trial design and the resources available to investigators and industry for clinical trial planning and conduct.
  • DMD Projects Reviewed:
    • Dr. Sachs, Rose Pharmaceuticals, USA, submitted the proposal ‘Therapy for Muscular Dystrophy by Inhibition of Mechanosensitive Ion Channels’ which was reviewed on 15th January 2011. REVIEW

Canadian DMD National Bone Health Research Initiative

  • Funding Type: Meeting Grant
  • Amount: $37,000
  • Year: 2011
  • Title: Canadian DMD National Bone Health Research Initiative
  • Details: Meeting Date(s) 29th - 30th September 2011
  • Meeting Location: Les Suites Hotel 130 Besserer Street Ottawa, Ontario K1N 9M9 Canada

Kathryn Wagner, Kennedy Krieger Institute

  • Funding Type: Supplement Grant
  • Amount: $35,000
  • Year: 7/2013 – 6/2014
  • Title: Enhancement of the muscle environment for stem cell transplantation
  • Abstract: Although skeletal muscle should be theoretically quite amenable to cell based therapies, such therapeutic development has lagged behind that of pharmacological therapies and gene therapy for Duchenne muscular dystrophy. This project focuses on enhancing the environment within the muscle for stem cell transplantation.

Second Annual NCH/Wellstone/OSU Myology Course, Columbus, OH. August 26-30, 2013

  • Funding Type: Meeting Grant
  • Amount: $22,182.66
  • Year: 2013
  • Title: Second Annual NCH/Wellstone/OSU Myology Course
  • Details: Meeting Date(s) 26-30 August 2013
  • Meeting Location: Nationwide Children's Hospital and Ohio State University, Columbus, Ohio
  • Meeting Goals: 

We propose a second annual one-week intensive course directed toward both clinically and laboratory-oriented post-doctoral trainees.  Faculty include recognized leaders in neuromuscular care and research, mostly among members of the Nationwide Children's Hospital/OSU Muscle Group. The target audience is international and we have received requests for enrollment from leading training programs in the United States and South America.

Each morning, attendees will receive lectures on neuromuscular disease genetics and pathophysiology. Each afternoon clinical trainees will receive didactic and hands-on training including but not limited to neuromuscular pathology, methods of clinical assessment, and cardiorespiratory care. Laboratory trainees will have a "wet lab" experience with hands-on training in muscle cell culture, muscle electrophysiology, and muscle precursor cell isolation. Each day will close with the two groups joining for a keynote lecture.

The program is designed to provide trainees with an integrated and intensive introduction to principles of neuromuscular disease.

  • Updates: Fifty-seven trainees attended, representing 27 different institutions and 5 different specialties. This is an increase in numbers and in geographic diversity in comparison to 2012 (when 39 attended, representing 13 different institutions). Notably, the 2013 course included attendees affiliated with institutions in Brazil and China.


Elliot Goldstein, DART Therapeutics

  • Funding Type: GIFTED
  • Amount: $300,000
  • Date: 6/2013 – 5/2014
  • Title: Clinical Development “Superhighway”: a program to create efficient drug development in DMD
  • Abstract:

The number of clinical trials on-going and planned in DMD patients has increased significantly in recent years and is expected to grow substantially over the coming 3-5 years as new therapies targeting not only the fundamental defects in DMD (e.g., exon-skipping, utrophin up-regulation), but also the associated pathologies such as fibrosis and muscle loss, are introduced into clinical drug development. Research projects and registries are underway in over 125 centers worldwide, many of which are putting further strain on clinical sites and demands on DMD patients.

Given the emerging plethora of potential new therapies for clinical development and the relative rarity of subjects appropriate for individual trials, a consistent and streamlined approach is urgently needed to achieve cost-effective and timely drug development in this area of very high unmet need. Furthermore, it is also important to ensure that those patients who may benefit from participation in a clinical trial for which they are qualified candidates are given the opportunity to do so.

The overall objective of this project is to achieve time and cost effective development of drug therapies for regulatory approval in DMD and related pediatric neuromuscular disorders. The deliverables of the Phase A of the Program Project will be a set of trial sites and clinical trial tools that can be utilized for any clinical study as a group or in part. Through the automation of common operational elements of DMD clinical trials we aim to reduce the cost and time from trial implementation to drug approval.  This project is co-sponsored by PPMD and DART Therapeutics.


Gregorij Kurillo, University of California at Davis

  • Funding Type: Exploratory Grant
  • Amount: $50,000
  • Date: 4/2013 – 3/2014
  • Title: Development of Novel Upper Extremity Outcome Measure in Duchenne Muscular Dystrophy
  • Abstract: In this proposal, we focus on meeting the critical need in the Duchenne muscular dystrophy (DMD) research field to develop a quantitative, robust, yet low-cost method for evaluating upper extremity function. Such methods will provide researchers with tools to better evaluate promising therapeutics in clinical trials, and ultimately facilitate development of effective treatments. In this project, we will develop and validate an innovative approach that utilizes a commercially-available and cost-effective portable motion capture system (Kinect) to provide detailed reachable workspace parameters as novel upper extremity outcome measures in DMD.
  • Publications: Technol Health Care. 2013 Jan 1;21(6):641-56. doi: 10.3233/THC-130764.

Evaluation of upper extremity reachable workspace using Kinect camera. Kurillo G, Chen A, Bajcsy R, Han JJ. http://iospress.metapress.com/content/m640m7k5736611u5/fulltext.pdf


Rita Perlingeiro, University of Minnesota

  • Funding Type: Investigator Grant
  • Amount: $220,000
  • Date: 3/2013 – 2/2015
  • Title: Duchenne Muscular Dystrophy: iPS Cells and Therapeutic Applications
  • Abstract: There has been tremendous excitement for the therapeutic potential of skin reprogrammed iPS cells in treating genetic diseases. This application builds on our successful studies testing cell therapies in mouse models of muscular dystrophy. Our goal now is to apply this technology to iPS cells obtained from DMD patients, to establish a method to genetically correct DMD, and to develop a GMP/clinically friendly protocol for the generation of iPS cells and their muscle derivatives


TREAT-NMD Advisory Committee for Therapeutics (TACT), 7th meeting, Baltimore MD, USA, 27-28 April 2013

  • Funding Type: Meeting Grant
  • Amount: $15,000
  • Date: 2013
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT)
  • Details: Meeting Date(s) 27-28 April 2013
  • Meeting Location: Baltimore, MD
  • Meeting Goals: 

TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases.

The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations that are necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

Two applications will be reviewed at the upcoming meeting, both concerend with Duchenne Muscular Dystrophy:

Peter Flynn, Fate Therapeutics Inc, San Diego, CA, USA: Proposal for Wnt7a-Analog Protein Therapeutic for the Treatment of Muscular Dystrophy
Jon Tinsley, Summit Corporation plc, Abingdon, UK: Proposal for clinical development of SMT C1100, a utrophin modulator for the treatment of Duchenne muscular dystrophy

 

 

Dr. Ron Victor, Cedars Sinai Medical Center, Tadalafil/Sildenafil Study for muscle and heart function in DMD

  • Funding Type: PPMD Investigator Award
  • Amount: $753,625
  • Date: 4/2011 - 3/2013
  • Title: DMD Tadalafil and Sildenafil Titration Protocol Research Grant
  • Major New Hypothesis: PDE5A inhibition, which boosts NO-cGMP signaling, will relieve functional muscle ischemia and restore normal blood flow regulation (i.e., functional sympatholysis) during exercise in boys with DMD. Our specific aim is to perform an efficient dose-titration study to inform the design of a randomized multi-center trial of PDE5A inhibition for clinical skeletal muscle and cardiac endpoints.
  • Abstract: Duchenne and Becker muscular dystrophies (DMD, BMD) are congenital X-linked muscle wasting diseases leading to shortened median life expectancies of 20 years in patients with DMD and of 50 years in patients with BMD. Two decades have passed since dystrophin was found to be the disease-causing gene in both conditions. Despite this knowledge and an explosion of basic research using elegant mouse models, clinical research has not kept pace and we still have no specific treatment for these patients. Our previous work—parallel translational experiments in mouse models and patients with muscle diseases including DMD—showed that loss of sarcolemmal nitric oxide synthase (nNOS), a dystrophin-associated protein, renders the diseased muscle fibers susceptible to functional ischemia and implicated skeletal muscle-derived nitric oxide (NO) as a novel therapeutic target for these refractory conditions. Specifically, we showed that skeletal muscle derived NO normally modulates adrenergic vasoconstriction in exercising skeletal muscle, a protective mechanism (“functional sympatholysis”), which is defective in the mdx mouse, the nNOS null mouse, and boys with DMD leading to functional muscle ischemia. Subsequently, several groups have shown that genetic and pharmacologic strategies that enhance NO signaling can ameliorate many features of the dystrophic phenotype—at least in mice, zebra fish, and drosophila. Recently, in the mouse model of DMD/BMD, acute administration of phosphodiesterase (PDE5A) inhibitors, which prolong the half-life of cGMP—the downstream target of NO in vascular smooth muscle—ameliorated muscle ischemia, muscle edema, and muscle fatigue after an acute bout of exercise. However, the dose of the PDE5A inhibitor in the mouse experiments was huge, and a key question is whether a clinical dose will be effective. We now propose parallel translational experiments in boys with DMD.
  • Press Release:  Parent Project Muscular Dystrophy Awards $750,000 Grant to Sildenafil/Taladafil Study
  • Recruitment Information:  This study is currently recruiting participants. Learn more. 
  • Progress Report:  A phase III study of tadalafil (Cialis™) in Duchenne by Eli Lilly and Company will start recruitment soon. More information.


Dr. Stanley Nelson, University of California, Los Angeles

  • Funding Type: Wellstone Center Supplemental Funds [Supplement to University of Pennsylvania Wellstone Center Grant]
  • Amount: $262,499
  • Date: 1/2011 - 12/2015
  • Title: RNA_SEQ Analysis for modifiers of fibrosis
  • Abstract: This subproject of the UPENN/University of Chicago/UCLA Wellstone Center will perform detailed RNA and DNA sequence analysis from mouse models to identify genes that modify the severity of fibrosis in muscular dystrophy.  This is a collaboration between the McNally Lab at the University of Chicago and the Nelson Lab at UCLA, and has two major components. The McNally lab is mapping gene variants that promote or reduce fibrosis in a mouse model of muscular dystrophy using inbred mouse strains.  The Nelson Lab will prepare sequencing libraries from the RNA samples to perform paired end sequencing of 30 million reads from each muscle/strain parental sample and will search the DBA genome for all variants within the linkage interval are present relative to the 129 genome. These data have been generated from next generation sequencing in collaboration with the Williams Lab at the University of Tennessee.

Peter Arthur, University of Western Australia

  • Funding Type: Exploratory Grant
  • Amount: $49,998
  • Date: 11/2013 - 10/2014
  • Title: Preclinical testing of procysteine for reducing dystropathology in the mdx mouse model of Duchenne Muscular Dystrophy
  • Abstract: For Duchenne muscular dystrophy, the underlying genetic defect is now well understood, although the precise molecular mechanisms leading to muscle pathology remain unclear. While much effort is directed at molecular therapies to correct the gene defect in DMD, this remains an expensive intervention yet to be used routinely in humans. In the interim, repurposed pharmaceutical compounds may offer a readily available, cost effective and expedient potential treatment option. In this context, we propose further testing of procysteine because it is already approved for ongoing human use and is relatively stable, inexpensive and can be taken orally.

The Eureka Institute for Translational Medicine Certificate Course

  • Funding Type: Investigator Grant
  • Amount: $100,000
  • Year: 2013
  • Title: The Eureka Institute for Translational Medicine Certificate Course
  • Details: Meeting Date(s) 11-17 May 2014
  •  Meeting Location: Sicily, Italy


Meeting Goals:
The objective is to establish the “Eureka Network-Duchenne” (END: as in “END DUCHENNE”). The long-term goal is for clinicians, scientists and advocates to build and maintain a highly productive team-based network for rapid exchange of data and ideas focused on issues related to Duchenne Muscular Dystrophy in the broadest sense.

The Eureka course is directed towards biomedical professionals in the early stages of their careers. Previous participants have been approximately equal numbers of PhD and MDs (or MD/PhDs) supplemented with biomedical administrators and industry scientists. Over the intensive 7-day course, participants examine case studies, attend highly focused seminars presented by members of the scientific, medical and biomedical regulatory communities and develop creative and novel problem-solving strategies to build uniquely effective teams. Participants also hone their abilities to communicate effectively across broad audiences. The program is tailored to individual needs, and is based on learner-centered discussions and mentoring by internationally recognized leaders.

Subha Raman, Cincinnati Children's Hospital Medical Center

  • Funding Type: Investigator Grant
  • Amount: $52,500
  • Date: 11/2012 - 10/2015
  • Title: Early Treatment with Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy- 2 year extension trial
  • Abstract: We are finishing a 1-year double-blind, randomized controlled trial of eplerenone vs. placebo in addition to an ACE inhibitor or ARB medication for boys with Duchenne muscular dystrophy. Because the effect of the medication may not be detectable within 12 months, we will extend the study in an open-label fashion. This means that all boys in the study would be given eplerenone in addition to the ACEI or ARB they are already taking, and be followed up for 2 years after completing the double blind trial.

ENMC workshop 204 - Biomarkers in DMD: from the discovery to the development toward clinical application and translation in other NMDs

  • Meeting Title: Biomarkers in DMD: from the discovery to the development toward clinical application and translation in other NMDs
  • Meeting Date: 1/24/2014 - 1/26/2014
  • Meeting Location: NH Hotel, Naarden, The Netherlands
  • Meeting Goals: The workshop aims at providing a comprehensive overview on biomarker research in DMD, highlighting some established and yet unpublished data, favouring data sharing, aimed at data validation based on a wider collaboration.
    The workshop will increase cooperative and harmonised effort in designing common research plans, addressing relevant issues in biomarker discovery and development, and bridging clinical measures and biomarkers research.

    These tasks will be afforded taking into consideration the Regulatory Authorities (FDA, EMA) views, the parents’ association hopes and needs and dialoguing with Industries. The outcome of the workshop should include the proposal for an optimised flowchart for biomarker discovery, validation and qualification in DMD, to lead to further prospective collaborative grants.
    All the experts participating in the WS are working in this field, and the involvement of basic researchers, clinicians, industries, parent associations and regulatory authorities should ensure high translatability of the meeting output into the clinical and pharmaceutical practice. In order to maximise the success of the workshop the focus will be on Duchenne muscular dystrophy as a prototype for this field, but the discussion will also include research in other NMDs, including the translatability of DMD existing biomarkers in other NMDs.
    Representative of Industries, EMA and FDA, and parents association will be invited.
  • Update: Meeting Summary: Biomarkers are defined as cellular, biochemical, molecular alterations or features that are measurable in biological material and that can provide information on physiological or pathological processes. Biomarkers may be used in differential and early diagnosis, and in monitoring of disease progression, regression, or therapeutic response. Duchenne Muscular Dystrophy (DMD) is a severe hereditary muscle disorder due to a wide variety of dystrophin gene mutations and presenting with variable clinical severity.
    Recently novel experimental drugs have been developed for DMD and several trials are ongoing, raising the urgent need of having fine tools for measuring the trial outcomes as well as for optimizing the selection of eligible patients. Biomarkers are appealing since may show earlier response to treatment and may not necessarily require invasive sampling, allowing their assessment at multiple endpoints.
    More at http://www.enmc.org/workshops/workshop-reports/biomarkers-dmd

Erica Reeves, Reveragen

  • Funding Type: Exploratory Grant
  • Amount: $49,991
  • Date: 11/2013 - 10/2014
  • Title: microRNAs as a modifier of exon skipping efficacy: feasibility of co-delivery
  • Abstract: Exon skipping has the potential to convert Duchenne to the milder Becker by acting as a molecular Band-Aid to restore dystrophin protein production. In exon skipping trials in both humans and dogs, the amount of resulting dystrophin produced was highly variable. Here, we present preliminary data to suggest microRNAs may cause this observed variability by partially blocking dystrophin protein production. This proposal outlines our experimental plan to combine the inhibition of dystrophin-targeting microRNAs with exon skipping.

TREAT-NMD Advisory Committee for Therapeutics (TACT), 8th Meeting, United Kingdom

  • Funding Type: Meeting Grant
  • Amount: $12,000
  • Date: 2013
  • Title: TREAT-NMD Advisory Committee for Therapeutics (TACT)
  • Details: Meeting Date(s) 1-3 November 2013
  • Meeting Location: University of Newcastle Upon Tyne, UK
  • Meeting Goals: TACT provides the neuromuscular community (clinicians, researchers, patient advocacy groups and industry) with independent and objective guidance on advancing new therapies (whether novel or repurposed) for neuromuscular diseases. The goal of each review is to position the potential therapy along a realistic and well informed pathway to clinical trials, and eventual registration, by evaluating the supporting preclinical data and all other critical drug development considerations that are necessary for objective decision-making and for the design and conduct of studies that generate meaningful data and have the potential to be funded longer term.

Three applications will be reviewed at the upcoming meeting, two concerned with Duchenne Muscular Dystrophy and one with inclusion body myositis.

1.‘Blockade of nitric oxide-related cell stress as potential treatment for inclusion body myositis’ Jens Schmidt PhD, University Medical Centre, Göttingen, Germany


2.‘NBD Therapy for Duchenne Muscular Dystrophy’ Denis Guttridge PhD, Ohio State University


3.‘Anti-GDF8 antibody for treatment of Duchenne Muscular Dystrophy’Carl Morris PhD, Rare Disease Research Unit, Pfizer Inc


2012 New Directions in Biology and Disease of Skeletal Muscle-New Orleans, LA

  • Funding Type: Meeting Support
  • Grantee: Dr. Lee Sweeney, University of Pennsylvania
  • See more


2010 New Directions in Biology and Disease of Skeletal Muscle-New Orleans, LA

  • Funding Type: Meeting Support
  • Grantee: Dr. Lee Sweeney, University of Pennsylvania
  • See more


2008 New Directions in Biology and Disease of Skeletal Muscle-New Orleans, LA

  • Funding Type: Meeting Support
  • Grantee: Dr. Lee Sweeney, University of Pennsylvania
  • See more


2006 New Directions in Biology and Disease of Skeletal Muscle-New Orleans, LA

  • Funding Type: Meeting Support
  • Grantee: Dr. Lee Sweeney, University of Pennsylvania
  • See more


2004 New Directions in Biology and Disease of Skeletal Muscle-New Orleans, LA

  • Funding Type: Meeting Support
  • Grantee: Dr. Lee Sweeney, University of Pennsylvania
  • See more

 

Back to Funding Portfolio

Facebook YouTube Twitter



Our family-centered approach is at the heart of everything we do. Learn more.

]]