Preclinical research of Tamoxifen

Using tamoxifen to improve muscle strength in Duchenne Muscular Dystrophy

Questions and Answers

What stage is this research?

This research in Duchenne is currently at the transition from pre-clinical to clinical, meaning that pre-clinical data and previous experience with this drug are sufficient to start a clinical trial involving patients. Tamoxifen is the generic name for an approved drug (Nolvadex, Tamifen) that is used to treat estrogen-dependent breast cancer.

Although it is possible that there will be an improvement in muscle strength in humans, we do not know for sure yet.

Where is this research being done and who is funding this research?

This research has been initiated at Dr. Urs Ruegg’s laboratory at the University of Geneva, Switzerland and is conducted by his collaborators, mainly Dr. Olivier Dorchies. It continues at Dr. Leonardo Scapozza’s laboratory. They have shown that tamoxifen triggers substantial improvements in muscle quality and strength in mdx mice. Among others, Parent Project Muscular Dystrophy has been helping to fund this research.

For details, see: Dorchies OM, Reutenauer-Patte J, Dahmane E, Ismael H, Petermann O, Patthey-Vuadens O, Comyn S, Gay E, Piacenza T, Handa RJ, Décosterd LA, and Ruegg UT: The anticancer drug tamoxifen counteracts the pathology in a mouse model of DMD. Am J Pathol. 182, 485-504 (2013).

Additional data, still unpublished, support the beneficial actions of tamoxifen on the mouse model of DMD.

What is the goal or purpose of this research?

The main goal is to initiate a clinical trial of tamoxifen in Duchenne patients based on convincing pre-clinical data. These showed that low doses (threshold 0.3 mg/kg body weight per day) were effective to improve muscular function in mdx mice.

What is the current state of this research?

Drs. Ruegg and Dorchies have tested various doses of tamoxifen in both young and old mice. Benefits of treatment included lower creatine kinase levels, 40% less fibrosis (scarring) in diaphragm and heart than in untreated mice, and near normal improvements in muscle strength. Although mice are not humans and it is never entirely certain how results will translate, a robust treatment response in mice that lack dystrophin is the gold standard for moving drugs into human clinical trials for Duchenne.

The laboratory of Dr. Dominic Wells at the University of London has shown that the results from Drs. Ruegg and Dorchies can be reproduced readily and that the combination of tamoxifen plus prednisolone gives a slightly stronger effect than any of the two drugs alone.

Starting in October 2015, Dr. Talya Dor from the Hadassah Medical Center in Jerusalem has given tamoxifen at doses of 10 and 20 mg per day to three Duchenne boys. All patients showed an initial improvement in strength, which stabilized after a few months and stayed stable since then. One boy showed an improved 6-minute walk test, and another one showed an improved 4-stair up score compared with his entry score. Creatine kinase levels were reduced mildly in two patients and dramatically in one and no significant adverse effects were noted. Parents of all boys reported higher energy and less fatigue, that were sustained throughout the 18-months treatment period. Based on these findings with compassionate off-label treatment with tamoxifen, Dr. Dor has started a formal clinical trial in Israel with boys aged 6-16 years to be treated for one year with a potential for extension to 3 years.

What steps need to be completed before moving into a clinical trial?

While pre-clinical data are encouraging, we don’t yet know if tamoxifen will have the same beneficial effects in Duchenne patients.

Noteworthy, the pharmacological profile of tamoxifen is well known; it has also been given to children aged 5 to 12 to treat hormone-dependent disorders, and no adverse effects have been reported.

A proposal for a clinical trial in Duchenne boys has been accepted in 2016 by the European Union E-Rare program termed “Clinical research for new therapeutic uses of already existing molecules (repurposing) in rare diseases”: This trial is also funded by several patient organizations (Duchenne UK, Duchenne Parent Project-NL, and Monaco Muscular Dystrophy Association).

A 48 week randomised, double-blind, placebo-controlled clinical trial with about 100 ambulant (6.5-10 year old) Duchenne patients under stable standard treatment of care with glucocorticoids is foreseen.

A presentation followed by a discussion with the experts of the TREAT-NMD TACT committee ( took place in late April 2017; the feedback is available under the TACT section of the TREAT-NMD website.

What is your best estimate for the length of time it will take to move this research into clinical trials?

The trial will start in June 2018, provided that ethical and regulatory permissions are in place.

The trial will be conducted in around ten centers in Europe. The Principal Investigator is Professor Dirk Fischer at the University Hospital in Basel, Switzerland.

Who would be eligible to participate in a clinical trial?

The inclusion criteria will be boys with Duchenne of age 6-12 years that are under stable standard treatment of care with glucocorticoids.

Where can I learn more about this research?

Details of this clinical trial will be posted on once it is ready to be initiated.

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