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Losartan

Updated 1/7/2011

The Therapeutic PipelineTherapeutic Pipeline: Losartan

Strategy

Losartan, an ACE inhibitor that lowers blood pressure (sold under the brand name of Cozaar), reduces the production of a molecule called TGF-beta, which is thought to interfere with the ability of muscle to repair itself from damage. The hypothesis for Duchenne is that using losartan to block TGF-beta will allow the muscle that is damaged due to the loss of dystrophin to better repair that damange and increase muscle strength.

In a single study, when mice that lacked dystrophin were treated with losartan their muscle fibers got bigger and the fibers were more resistant to fatigue caused by muscle contraction (see Publications, below).

ACE inhibitors have commonly been used to treat cardiomyopathy in Duchenne—the ability of losartan to treat cardiomyopathy compared to lisinopril, a common ACE inhibitor, is being tested now (see Clinical Trials, below).

Progress

Nationwide Children’s Hospital is conducting a clinical trial that will compare the effects of Cozaar (losartan) with Prinivil or Zestril (brand names for lisinopril, an ACE-inhibitor) on skeletal and cardiac muscle function. The investigators are seeking to enroll 150 participants with Duchenne who have a cardiac "ejection fraction" of less than 55 percent and who are not taking any other cardiac medications. Furthermore, in February of 2010 a proposal to conduct a clinical study of losartan in Duchenne from Childrens National Medical Center in Washington DC was reviewed by TREAT-NMD’s TACT committee.

Clinical Trials

Publications

Cohn RD et al. Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states.  Nat Med. 2007 Feb;13(2):204-10. Epub 2007 Jan 21. Erratum in: Nat Med. 2007 Apr;13(4):511.
Chamberlain JS et al. ACE inhibitor bulks up muscle. Nat Med. 2007 Feb;13(2):125-6. No abstract available
  • Cohn RD et al. Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states.  Nat Med. 2007 Feb;13(2):204-10. Epub 2007 Jan 21. Erratum in: Nat Med. 2007 Apr;13(4):511.
  • Chamberlain JS et al. ACE inhibitor bulks up muscle. Nat Med. 2007 Feb;13(2):125-6. No abstract available

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Related links

Johns Hopkins release on mouse data
TREAT-NMD TACT review of an application from Dr. Spurney at Childrens National Medical Center to test Losartan in Duchenne

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