Clinical Trials and Studies March-April 2007

Article Highlights:

News on clinical trials and studies as of February 2007

by Quest Staff on March 1, 2007 - 2:47pm

QUEST Vol. 14, No. 2

This article includes items about clinical trials in: Duchenne MD, limb-girdle MD, distal muscular dystrophy, and acid maltase deficiency.

PTC124 to be tested at higher doses in DMD

New Jersey company PTC Therapeutics will test a higher dose of its experimental compound PTC124 in approximately 12 boys with Duchenne muscular dystrophy (DMD) caused by a premature stop codon mutation. The drug is designed to coax muscle cells to ignore these mutations and make functional dystrophin.

In October, the company announced that, in a trial of 26 boys with DMD, the drug appeared safe and well tolerated. Results showed significant decreases in serum creatine kinase (CK), which leaks out of damaged muscle tissue, and increases in dystrophin.

In the higher-dose study, boys will take the drug at 20 milligrams per kilogram of body weight at breakfast and lunch and 40 milligrams per kilogram at dinner for 28 days. They’ll be followed closely for an additional 28 days and periodically after that.

Contact Kerri Donnelly at PTC Therapeutics at (908) 222-7000, ext. 112, or

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Multinational trial to evaluate steroids in DMD

Some 300 boys with Duchenne muscular dystrophy (DMD) may soon be invited to participate in a multinational, multiyear study of three corticosteroid medication regimens.

Although corticosteroids such as prednisone have been used for many years to slow the course of DMD, and have been recommended by the American Academy of Neurology since 2005, there remains much debate about which steroids to use, how much to give, on what schedule and for what length of time.

Set to launch in 2008, with funding from the U.S. National Institutes of Health, the trial is expected to encompass approximately 59 sites in 11 countries.

Kate Bushby, professor of neuromuscular genetics at the International Centre for Life in Newcastle Upon Tyne, United Kingdom, and Robert Griggs, professor of neurology at the University of Rochester (N.Y.) Medical Center, are the principal investigators.

The doctors will test three regimens, using prednisone and deflazacort, in boys 4 to 7 years old for at least three years. They’ll compare the children’s muscle and respiratory functions, and their parents’ satisfaction with the treatment.

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LGMD gene transfer trial still has a few slots

A gene therapy trial for alpha-sarcoglycan-deficient limb-girdle muscular dystrophy (LGMD) is close to starting, says principal investigator Jerry Mendell at Columbus (Ohio) Children’s Research Institute. There are a few slots open for additional patients.

In the first phase of the trial, an alpha-sarcoglycan gene will be injected into a leg muscle to test the safety of the procedure.

“These initial gene therapy trials lay the foundation for moving to the next level of gene transfer, where the gene can be given through the circulation to reach many muscles,” Mendell said.

The investigators are seeking people with known alpha-sarcoglycan deficiency, but will work with those who don’t know what type of LGMD they have.

Contact Xiomara Rosales-Quintero, Columbus Children’s Research Institute and Gene Therapy Center, at (614) 722-6961 or

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Large study identifies common U.S. LGMD types

The first large-scale study to assess the relative frequency of different types of limb-girdle muscular dystrophy (LGMD) has found that the most common LGMDs in the United States involve deficiencies of calpain, dysferlin, sarcoglycans and dystroglycan.

The study, supported in part by MDA, drew participants from six MDA clinics.

The investigators, who published their results in the October issue of the Journal of Neuropathology and Experimental Neurology, examined muscle samples from 266 people with diagnoses of LGMD based on symptoms and family history. They found a reduction or absence of the dysferlin protein in 18 percent; of a sarcoglycan in 15 percent; of dystroglycan in 15 percent; and of caveolin in 1.5 percent.

Protein abnormalities, however, don’t always correspond to gene abnormalities, because one gene abnormality can affect more than one protein. The researchers note that several new therapies on the horizon will require accurate protein and DNA diagnoses in LGMD.

The Jain Foundation, a group dedicated to research on dysferlin gene mutations, which can cause type 2B LGMD or Miyoshi myopathy, a type of distal MD, is urgently seeking participants for its patient registry, a database that it hopes will speed understanding of these disorders. To register online, go to, and click on Patient Registration. Or contact Plavi Mittal at All information will be kept confidential.

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Heart health studied in carriers of DMD, BMD

A questionnaire-based study of beliefs and practices related to cardiac health in genetic carriers of Duchenne and Becker muscular dystrophies (DMD, BMD) closed Dec. 31. The study, funded by the U.S. Centers for Disease Control and Prevention, also asked about the impact of the disease on the lives of carriers and their families.

A total of 1,348 women submitted usable research data, which are being analyzed.

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Various factors may affect Pompe’s severity

It looks like there’s more to predicting the severity and onset of acid maltase deficiency (AMD), or Pompe disease, than knowing the makeup of a person’s acid maltase genes.

Arnold Reuser at Erasmus Medical Center-Rotterdam, the Netherlands, with colleagues at other Dutch institutions, and Genzyme, a Massachusetts pharmaceutical company, studied 98 people with Pompe disease. All of them had a common AMD mutation in one of their two acid maltase genes and a highly deleterious mutation in the other acid maltase gene.

The common mutation allows production of about 10 percent of the normal level of the enzyme acid maltase. The researchers selected patients whose second acid maltase gene led to no enzyme production.

The onset and course of the disease varied in these study participants far more than the investigators had anticipated. The age of symptom onset varied from less than a year to 52 years; the age of first wheelchair use ranged from 18 to 64 years; and first ventilator use from 14 to 68 years.

The authors, who published their findings in the Jan. 9 issue of Neurology, say that, when some acid maltase can be made, other genes or environmental factors influence disease severity. For example, a study published in the Jan. 9 issue of Muscle & Nerve showed that a high-protein, low-carbohydrate diet, coupled with daily treadmill exercise, can stabilize or even improve muscle function in at least some adult-onset Pompe patients.

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