Clinical Trials and Studies July-August 2007

Article Highlights:

Updates on clinical trials and studies as of June 2007

by Quest Staff on April 1, 2007 - 10:16am

QUEST Vol. 14, No. 4

Canadian team will pursue cell transplants in men with DMD, BMD

Jacques Tremblay at Laval University in Quebec City says he has obtained permission from Health Canada to conduct a clinical trial to see whether transplantation of muscle precursor cells (MPCs) can improve the strength of an arm muscle in 10 men with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) who are at least 18 years old.

Tremblay, who received MDA support to develop laboratory procedures associated with MPCs in the late 1990s and in 2004, has previously shown that dystrophin (the protein needed in DMD) was produced in the muscle fibers of eight out of nine patients who received transplantations of this type of cell.

The new trial will use a technique his lab developed called high-density cell transplantation, which allows millions of cells per square centimeter to be injected at a time.

In January, in the journal Neuromuscular Disorders, Tremblay’s group reported they’d used the high-density technique successfully in a 26-year-old man with advanced DMD, who tolerated the procedure well and may have benefited from it.

They used cells that were isolated from an arm muscle of the patient’s father and then coaxed in the lab toward becoming muscle, but they weren’t fully mature. They then injected 67.5 million MPCs per square centimeter into a lower leg muscle, 55 million per square centimeter into the area below the thumb, and 25 million per square centimeter into the biceps muscle.

The patient, who was given the immunosuppressant drug tacrolimus (Prograf) to prevent rejection of the cells, said he found the injections were more tolerable than the average dental procedure.

A year and a half after the transplant, some 35 percent of the injected muscle fibers in the leg were making dystrophin. In the biceps, where there was more scar tissue, there were only a few fibers left, two of which were making dystrophin.

The only functional improvement the team saw was a significant increase in the patient’s ability to move his thumb. They say this may have been a placebo effect [a favorable response to a treatment because the patient believes in it], since the subject knew he was receiving MPCs.

The new trial, Tremblay notes, will be “blinded,” meaning one arm will get MPCs and the other a salt solution. Neither the investigators nor the participants will know which arm got which preparation.

Tremblay says progress in his lab can be followed at

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NIH opens two new SMA trials

Two National Institutes of Health-sponsored, multicenter studies of sodium phenylbutyrate in spinal muscular atrophy (SMA) have opened. One will enroll up to 30 babies with type 1 SMA who are 2 months to 2 years old, and the other will enroll up to 30 participants with type 2 or 3 SMA who are 2 to 12 years old.

Preliminary evidence from laboratory studies and a pilot trial suggests that sodium phenylbutyrate may increase levels of the SMN protein, which is needed but deficient in SMA. For details, contact Barbara Driver at (301) 738-3698 or

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IVIG treatment benefits those with worsening MG

A clinical trial to test the effectiveness of intravenous immunoglobulins (IVIG) in treating myasthenia gravis (MG) has provided what the investigators say is the “first reliable evidence for the effectiveness of IVIG in patients with MG and worsening weakness.”

In MG, the immune system mistakenly attacks components of the neuromuscular (nerve-to-muscle) signal transmission system, resulting in fluctuating weakness that can be severe. It’s generally treated with drugs that prolong the action of a chemical carrier of nerve signals and/or with those that suppress the immune system.

Two other treatments, less often used, are plasmapheresis, which removes the offending immunoglobulins from the blood; and, somewhat paradoxically, immunoglobulin infusion (IVIG), which adds pooled immunoglobulins from donors. The added immunoglobulins are thought to redirect the immune system.

Lorne Zinman at Sunnybrook Health Sciences Center in Toronto, and colleagues, who published their findings in the March 13 issue of Neurology, randomly assigned 51 adults with MG and worsening weakness to receive a two-day infusion of either IVIG or an inactive solution (placebo).

Two weeks later, 25 percent of the IVIG group showed improvement, compared with 6 percent of the placebo group. None of those who received IVIG worsened, while 4 percent of those on placebo did.

Functional changes were relatively small. They were the most meaningful in those with moderate to severe MG, compared to those with mild symptoms. Onset of the effect was rapid compared with the usual response to medications.

There were no serious side effects or adverse events.

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Researchers share new findings at AAN meeting

The 59th annual meeting of the American Academy of Neurology (AAN) took place April 28-May 5 in Boston and included several presentations relevant to people with neuromuscular disorders. Summaries of a few of them follow. (For a complete report, see “What’s New.”)

Alemtuzumab shows promise in IBM

An immunosuppressant medication called alemtuzumab (Campath), approved to treat a form of chronic leukemia, may have promise in treating inclusion-body myositis (IBM), a muscle disease that’s characterized by both inflammation and degeneration.

Marinos Dalakas at the National Institutes of Health, and colleagues, gave alemtuzumab to 13 IBM patients for four days at 0.3 milligrams per kilogram per day and saw an average strength increase of 8 percent four months later and 4 percent six months after treatment. Six of the 13 participants experienced strength increases averaging 16 percent and reported improvement in activities of daily living. The other seven declined by 6 percent.

High-dose vitamin C not helpful In 12 people with CMT1A

High-dose ascorbic acid (vitamin C) was neither well tolerated nor beneficial in a small study in people with type 1A Charcot-Marie-Tooth disease (CMT1A).

In a one-year study of 12 people with CMT1A who received 5 grams per day of ascorbic acid, six tolerated the dose for the whole year, five developed gastrointestinal side effects that required lowering the dose, and one discontinued the medication because of general malaise. No significant differences in symptoms or electrophysiological measurements before and after treatment were detected in anyone.

Drug combination didn’t help in MG

Adding the immunosuppressant drug mycophenolate mofetil (CellCept) to prednisone, a more commonly used immunosuppressant, didn’t improve strength, activities of daily living or any other measurement in people with myasthenia gravis (MG) after three months of treatment. Eighty people with MG, a disorder in which the immune system mistakenly attacks the nerve-muscle junction, took prednisone at 20 milligrams a day, plus either 2.5 grams a day of mycophenolate mofetil or a look-alike placebo (inert substance).

The investigators speculated that the lack of difference in the two groups could be due to a greater-than-predicted benefit from the prednisone alone or the short duration of the study.

Anti-androgen drug may improve strength in SBMA

A drug that reduces levels of the male hormone testosterone (an androgen) has shown promise in the treatment of spinal-bulbar muscular atrophy (SBMA, or Kennedy’s disease), in which a mutation in the gene for the androgen receptor protein causes progressive weakness. In this study from Japan, four patients received injections of goserelin (Zoladex) every three months. Three of the four improved in either strength or speed of nerve signal conduction or both.

The investigators said a larger study was needed to confirm the effectiveness of this drug.

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