Research Briefs: DMD, Leigh Syndrome, MG, Periodic Paralysis, Pompe Disease

Drug testing for Duchenne MD, Leigh syndrome and Pompe disease moves forward; and two MDA-supported mouse studies suggest leads for myasthenia gravis and periodic paralysis

Article Highlights:
  • Duchenne muscular dystrophy: Recent developments include an experimental androgen receptor modulator and a potential antifibrotic drug, and a utrophin modulation program moves ahead.
  • Leigh syndrome: An April 5, 2013, webinar will discuss development of a new drug.
  • Myasthenia gravis: A drug that works on the immune system's complement cascade improved muscle strength in mice.
  • Hypokalemic periodic paralysis: Butenamide prevented episodes of weakness in mice.
  • Pompe disease: An experimental drug for late-onset Pompe disease is in testing.
by Margaret Wahl on March 26, 2013 - 4:21pm

Drug development and identifying new leads for possible drug development are in the news for five neuromuscular diseases in MDA’s program.

DMD: Building muscle, fighting inflammation

Update (May 16, 2013): Information about a forthcoming trial of HT-100 can be viewed at Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of HT-100 in Duchenne Muscular Dystrophy.

DART Therapeutics announced March 20, 2013, that it will develop an experimental compound called DT-200 for the treatment of Duchenne muscular dystrophy (DMD).

DT-200 is a selective androgen receptor modulator (SARM), a type of compound that may promote increased muscle mass and strength. This type of compound does not target a specific genetic mutation.

The biotechnology company says it plans to start a phase 2 study in adults with normal muscles in the second half of 2013, followed by a study in people with abnormal muscles and ultimately a study in children with DMD or other neuromuscular disorders if the results are promising.

See DART Therapeutics Develops Drug Candidate for Duchenne Muscular Dystrophy, a press release from DART published March 20, 2013.

In addition, DART is developing another experimental DMD drug, HT-100, through its affiliate Halo Therapeutics, that works through an entirely different mechanism from DT-200. HT-100 is being developed to reduce fibrosis and inflammation in muscle tissue and promote healthy muscle fiber regeneration. Its mechanism of action theoretically could be applied to DMD caused by any genetic mutation.

See European Medicines Agency Grants Orphan Medicinal Product Designation, a press release from Halo Therapeutics published May 3, 2012.

DMD: Boosting utrophin

Drug discovery and development company Summit PLC, based in Oxford, United Kingdom, announced March 21, 2013, that it plans to begin a clinical trial of its lead experimental utrophin-boosting drug SMT C1100 in people with Duchenne muscular dystrophy (DMD) during the second half of 2013, and to continue experimenting with "next-generation" utrophin modulators that are at an earlier stage of development.

Utrophin is a muscle protein similar to dystrophin, which is missing in DMD. Unlike dystrophin, utrophin is produced — albeit in small amounts — by people with and without DMD. Raising utrophin levels may be therapeutic in this disease, and utrophin-based therapy may be less likely to elicit the unwanted immune response that has been seen with dystrophin-based therapy in dystrophin-deficient patients. Utrophin modulators could, theoretically, be used to treat DMD resulting from any dystrophin gene mutation.

In December 2011, MDA awarded an MDA Venture Philanthropy (MVP) grant to Summit for development of utrophin-modulating therapies for DMD. So far, SMT C1100 has been tested and found safe in healthy human volunteers, but has not been tested in people with DMD.

For more information, see:

Leigh syndrome: Webinar to discuss drug development

An update from Edison Pharmaceuticals on development of and trials to test the experimental drug EPI-743 in children with Leigh syndrome, a mitochondrial myopathy, will take place as a Web-based event on April 5, 2013, at 12:45 p.m. Eastern. It's expected to last 90 minutes.

To join the online event, go to UMDF-Mito Action EPI-743 Webinar. To hear the audio portion by phone in the U.S. or Canada, call (650) 479-3207 and enter access code 667 321 101.

Questions can be sent in advance to or

For more information, see:

MG: Blocking 'complement'

MDA grantee Premkumar Christadoss at the University of Texas Medical Branch in Galveston, and colleagues, found that treating mice that have a disorder resembling myasthenia gravis (MG) with a molecule that blocks activation of part of the immune system improved muscle strength and preserved important structures at nerve-to-muscle junctions.

The part of the immune system blocked in these experiments is called the complement cascade, activation of which is a factor in human MG. The study results indicate that blocking the complement cascade has therapeutic potential in this disease.

See Complement C2 siRNA-Mediated Therapy of Myasthenia Gravis in Mice, a summary of a scientific paper in the Journal of Autoimmunity, published Feb. 11, 2013. (Fee required to download complete paper.)

Periodic paralysis: Bumetanide prevented weakness in mice

A drug called bumetanide prevented attacks of weakness or paralysis in mice with a condition mimicking hypokalemic periodic paralysis caused by a sodium channel mutation, reports MDA grantee Stephen Cannon at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

About 20 percent of people with hypokalemic periodic paralysis have a mutation in the gene for a structure known as a sodium channel; about 60 percent have a mutation in a calcium channel gene, and about 20 percent have undetermined mutations.

When the mice were exposed to hypokalemic conditions, bumetanide was more effective at preventing weakness than was acetazolamide, a standard treatment for hypokalemic periodic paralysis. Bumetanide is approved as a prescription medication for the treatment of fluid retention and is marketed under the name Bumex.

For more information, see Bumetanide Prevents Transient Decreases in Muscle Force in Murine Hypokalemic Periodic Paralysis, a summary of a scientific paper in Neurology, published Feb. 20, 2013. (Complete article available for a fee or with a paid subscription.)

Pompe disease: Late-onset treatment moves forward

Update (May 16, 2013): This story was updated to reflect the existence of the phase 1/2 extension study for BMN-701.

Pharmaceutical company BioMarin announced March 19, 2013, that it plans to move to a phase 2/3 trial of its experimental drug BMN-701 for late-onset Pompe disease, pending a review by regulatory authorities.

The company said its phase 1/2 trial of the drug, now complete, "exceeded the company's pre-specified requirements for proceeding to the next phase of development." An extension study for those who have been in the phase 1/2 trial is being conducted.

BMN-701 is an enzyme replacement therapy that combines the GAA (acid maltase) enzyme, which is deficient in people with Pompe disease, with a protein called insulin-like growth factor 2 (IGF2).

BioMarin hopes to start a phase 2/3 trial of BMN-701 by the end of 2013 in people with late-onset Pompe disease who have been previously treated with the approved enzyme replacement therapies Myozyme or Lumizyme.

For more information, see:

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