Clinical Trials November-December 2007

Article Highlights:

The latest news on clinical trials and studies as of October 2007

by Quest Staff on November 1, 2007 - 1:12pm

QUEST Vol. 14, No. 6

Items in this article refer to clinical trials in: Duchenne muscular dystrophy, myasthenia gravis, Becker muscular dystrophy, limb-girdle muscular dystrophy, hypokalemic and hyperkalemic periodic paralysis, Pompe disease, FSH muscular dystrophy,  Miyoshi distal muscular dystrophy, myotubular myopathy, congenital muscular dystrophy and ALS.

10-year study suggests early ACE inhibitor treatment in DMD may prolong survival

A 10-year French study of 57 boys with Duchenne muscular dystrophy (DMD) who were ages 9 to 13 at study entry found that early treatment with the angiotensin-converting enzyme inhibitor perindopril is associated with a survival benefit. ACE inhibitors reduce stress on the heart and are part of standard therapy for cardiac muscle dysfunction (cardiomyopathy) from any cause.

MG Illustration
A French study suggests that treating boys with DMD with ACE inhibitors even before cardiac abnormalities appear improves survival.

Denis Duboc at Cochin Hospital in Paris, and colleagues, who published their findings in the September issue of American Heart Journal, randomly assigned 28 DMD patients with normal heart function to take 2 to 4 milligrams of perindopril per day; and another 29 patients, also with normal heart function, to take a placebo (inert substance).

After three years, there were no differences in cardiac function or survival in the two groups. Perindopril was then given to all study participants for up to 10 years.

At 10 years, 26 of 28 (93 percent) of the patients in the early perindopril group were alive, compared with only 19 of 29 (66 percent) who received a placebo for the first three years.

In the United States, the American Academy of Pediatrics recommended in 2005 that doctors consider using ACE inhibitors and/or another class of cardiac drugs, beta blockers, in children with DMD as soon as signs of cardiac dysfunction appear. However, use of ACE inhibitors or other medications before signs of cardiomyopathy are present is not yet standard treatment in French or U.S. clinics.

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Scientists in Israel and the United Kingdom announced in the Aug. 14 issue of Neurology that an experimental compound known as EN101 (also called Monarsen) appears to be safe and possibly effective in treating myasthenia gravis (MG).

EN101 is a so-called antisense molecule, designed to block the synthesis of the protein known as acetylcholinesterase (AChE). This protein is an enzyme that normally degrades acetylcholine, a carrier of signals from nerve to muscle.

In MG, a treatment goal is to increase acetylcholine action at the nerve-muscle junction to compensate for a mistaken attack on this area by the immune system. Interfering with AChE is one way to accomplish this.

Zohar Argov at Hadassah University Hospital in Jerusalem, with colleagues at other Israeli institutions and at Ester Neuroscience in Herzliya, Israel, and Hope Hospital in Salford, UK, gave oral EN101 to 16 people with MG in an open-label trial, meaning trial participants knew they were getting the experimental drug.

There were no serious side effects or adverse events.

Thirteen participants showed improvement in their quantitative MG score, which measures functional status, although few had clear clinical improvement, such as disappearance of eyelid weakness.

Fourteen of the participants reported subjective improvement with EN101 compared to their standard medication, pyridostigmine.

In an editorial in the same issue of Neurology, Henry Kaminski at Saint Louis (Mo.) University Medical Center writes that “this trial suggests a therapeutic benefit, which should bolster hope for this approach for drug development” not only for MG but for other diseases in which it’s desirable to block the synthesis of a protein.

He notes, “The present short-term study demonstrates safety in a small group of patients, but also a strong suggestion of efficacy.” He also found it encouraging that an antisense drug appears to be effective when given by mouth.

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Two meds for periodic paralysis will be tested

Investigators at the University of Rochester (N.Y.) Medical Center will compare the medications acetazolamide and dichlorphenamide to see which is better for preventing episodes of paralysis and improving strength in hyperkalemic or hypokalemic periodic paralysis.

Both drugs are in a class known as carbonic anhydrase inhibitors. This 252-participant study is seeking people with either type of periodic paralysis who experience an average of at least one episode of weakness per week but fewer than three per day.

Contact Patty Smith at (585) 275-4339 or

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New Myozyme studies to provide more data on Pompe disease treatment

Genzyme, the Cambridge, Mass., biopharmaceutical company that developed Myozyme, will continue to test this laboratory-engineered enzyme, which compensates for missing acid maltase, in people with Pompe disease (acid maltase deficiency).

A new study will test higher and more frequent dosing regimens of Myozyme in 12 patients who are at least 6 months old and have shown less than optimal improvement on the standard regimen, which is an intravenous infusion every other week of 20 milligrams of Myozyme per kilogram of body weight.

The company also will evaluate the long-term growth and development of patients with infantile-onset Pompe disease treated with Myozyme before they’re a year old.

For more information, contact Deya Corzo, senior medical director at Genzyme, at (800) 745-4447 or (617) 252-7832, or write to See also

Genzyme is also changing its method of supplying Myozyme to a new, large-scale process that isn’t yet approved by the Food and Drug Administration. In April, to minimize treatment disruption for people on Myozyme and help ensure that Myozyme is available to new patients who urgently need it, the company opened the Myozyme Temporary Access Program (MTAP). For more information, see, or call (800) 745-4447.

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Boston group will study molecular pathways in several muscle diseases

Investigators at Children’s Hospital in Boston (affiliated with Harvard University School of Medicine) are recruiting participants for a 500-person, long-term study of people with several types of muscle disease and their affected or unaffected close relatives. They’re seeking to uncover new genetic and biochemical pathways involved in these disorders.

They’re seeking people with a molecular diagnosis of Becker, Duchenne, facioscapulohumeral or Miyoshi distal muscular dystrophy, or myotubular myopathy. Participants with limb-girdle muscular dystrophy can have either a clinical or molecular diagnosis.

Contact Elicia Estrella at (617) 919-4552 or

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Anti-cell-death compound to be tested in CMD

Santhera Pharmaceuticals of Liestal, Switzerland (, announced in July that it will pursue development of omigapil, also known as SNT317, for congenital muscular dystrophy (CMD).

The company purchased the rights to develop the drug from Novartis, a multinational pharmaceutical firm that had hoped to develop omigapil for amyotrophic lateral sclerosis (ALS), after laboratory experiments showed it helped prevent cell death.

Novartis abandoned the ALS-related plan in 2005 after omigapil failed to show any benefit in that disease. (Novartis’ name for the compound was TCH346.)

In a July 2 press release, Santhera’s Chief Scientific Officer Thomas Meier said, “CMD refers to a group of genetically determined devastating neuromuscular diseases which frequently affect infants or newborn babies.

“Our preclinical research to date has shown that omigapil could reduce the progressive loss of muscle tissue, weight loss, skeletal deformations and early mortality in a disease-relevant model. Based on these data, we believe omigapil is a potential therapeutic option for CMD. Together with internationally leading clinical experts, we are currently defining the details of the clinical development plan.”

The company expects to start a trial before the end of 2008.

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Dysferlin deficiency can cause heart damage

On Sept. 9, researchers in Germany published a paper online in the Journal of Molecular Medicine showing that two out of seven patients they studied with type 2B limb-girdle muscular dystrophy (LGMD 2B) had cardiac muscle damage (cardiomyopathy), and an additional two showed some heart enlargement that the authors speculated may reflect an adaptive repair mechanism. Katrin Wenzel at the Charité, a Berlin medical center, and colleagues, recommended that people with LGMD be carefully evaluated for heart disease.

A deficiency of the dysferlin protein can cause either LGMD2B or Miyoshi distal muscular dystrophy.

MDA grantee Kevin Campbell at the University of Iowa in Iowa City, and colleagues, recently found that dysferlin participates not only in the repair of the membrane that surrounds each skeletal muscle fiber, but also in the repair of a membrane that surrounds each cardiac muscle cell.

Although cardiomyopathy had not previously been considered part of dysferlin deficiency, the Campbell report in the July issue of the Journal of Clinical Investigation suggested that it might be, especially when combined with strenuous exercise.

When the investigators studied dysferlin-deficient mice, they found the animals developed mild cardiomyopathy as they aged. Strenuous treadmill exercise worsened the damage.

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