Clinical Trials and Studies November-December 2006

Article Highlights:

The latest news on clinical trials and studies as of October 2006

by Quest Staff on November 1, 2006 - 2:24pm

QUEST Vol. 13, No. 6

This article contains news of clinical trials in: myasthenia gravis, limb-girdle muscular dystrophy, polymyositis, dermatomyositis, inclusion-body myositis, and unapparent forms of muscular dystrophy

Moving ahead in myasthenias

In myasthenias, disorders in which the transmission or reception of signals from nerve fibers to muscles is disrupted, treatment has long centered around improving the strength of the signal by prolonging the action of the chemical acetylcholine. In cases where the underlying problem involves a renegade immune system, treatment is also aimed at suppressing immune responses that interfere with neurotransmission. Investigators are refining these strategies to achieve more benefit with fewer side effects.

Value of thymectomy in MG being tested

A multinational trial to determine the value of removing the thymus as a treatment for myasthenia gravis (MG) has opened at some 70 centers in the United States, Europe and Asia.

Muscle Cell
At the junction of nerve and muscle cells, acetylcholine flows across a gap and lands on receptors, which transmit muscle contraction signals. Any part of the process can be disrupted, resulting in myasthenia.

Removing the thymus, an organ of the immune system located in the chest, involves surgery (thymectomy). It has long been used as a treatment for MG, a disorder in which the immune system mistakenly attacks the parts of muscle fibers that receive signals from the nervous system.

But until now, no systematic study has been conducted that measures what, if any, benefit there is for patients in adding thymectomy to standard MG medications, such as prednisone. This study is designed to determine whether thymectomy provides additional control of MG symptoms or reduces the amount of prednisone patients need.

The trial is seeking adults with MG who are between 18 and 60, are willing to be randomly assigned to receive prednisone and a thymectomy or prednisone alone, are willing to be studied for at least three years, and meet other criteria.

For details, see, or call Greg Minisman at the University of Alabama-Birmingham at (205) 934-4905.

New myasthenia drug under study

The drug Monarsen (formerly EN101), developed by Ester Neurosciences in Herzelia, Israel, is being studied in the United Kingdom under the direction of Jon Sussman at Hope Hospital in Greater Manchester. If all goes well, testing of the drug in people with myasthenias may be expanded to the United States and Europe.

People with myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LES) and some congenital myasthenic syndromes (CMS) benefit from drugs that prolong the action of acetylcholine at the junction of nerve and muscle fibers.

In MG, the immune system mistakenly attacks receptors for acetylcholine on muscle cells. In LES, the immune system inhibits the chemical’s release from nerve fibers. And in some CMS cases, the action of acetylcholine is insufficient because of a genetic mutation that affects the neuromuscular junction.

A common treatment for these diseases is pyridostigmine (Mestinon), which interferes with the breakdown of acetylcholine by the enzyme AchE. But pyridostigmine’s actions are limited, and, at high doses, it can have unwanted side effects.

Monarsen targets AchE before it’s synthesized, while pyridostigmine targets the finished protein. According to Ester Neurosciences, attacking the finished protein stimulates the body to produce more AchE, triggering a battle between the drug and the nervous system. In contrast, the company says, Monarsen, which inhibits AchE synthesis, doesn’t cause this vicious cycle.

The company says Monarsen also could have applications for amyotrophic lateral sclerosis (ALS), a disease in which muscle-controlling nerve cells die.

Sleep apnea in MG can lead to overmedication

A Canadian research group has found that a type of disturbed breathing during sleep resulting from obstruction of the airway is probably much more common in people with myasthenia gravis (MG) than in the general population. They say the problem, known as obstructive sleep apnea (OSA), may not always be correctly identified.

Michael Nicolle of the London Health Sciences Centre in Ontario, and colleagues, who published their findings in the July 11 issue of Neurology, randomly selected 100 people with MG from 400 clinic patients and assessed their risk of obstructive sleep apnea.

Fifty were identified as high-risk, and 37 agreed to undergo sleep studies. Of those, 34 were found to have OSA, mostly due to weakness of the mouth and throat muscles and mostly leading to episodes of abnormally slow, shallow breathing. Two people in the low-risk group were also found to have sleep apnea, yielding a total of 36 percent of MG patients in this study with this condition.

The prevalence of OSA in the general population is estimated at 15 percent to 20 percent. The researchers say 36 percent is an underestimate in MG, since 13 of the high-risk patients didn’t have sleep studies.

Sleep apnea can lead to sleep deprivation and significant daytime fatigue, which could be misinterpreted as resulting from overall worsening of the person’s MG, the authors say. They caution, “Without considering a role for OSA, a history of fatigue could lead to deleterious increases in corticosteroids.”

The correct treatment for obstructive sleep apnea is usually delivery of pressurized air by mask.

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LGMD gene transfer trial slated for next year

Neurologist Jerry Mendell, an MDA grantee at Columbus (Ohio) Children’s Research Institute (CCRI), says he hopes to start a clinical trial by mid-2007 that will test the safety of transferring the gene for alpha-sarcoglycan into leg muscles of people with type 2D limb-girdle muscular dystrophy (LGMD2D).

The trial, which is open to LGMD2D patients ages 5 and older, is under the auspices of the National Institutes of Health, MDA and CCRI. Those who think they may have LGMD2D can apply for the trial and undergo DNA testing of their blood cells in Columbus. If they meet study criteria, they may be asked to undergo a muscle biopsy as well.

The trial will last three months, and some help with travel expenses may be available. For information, contact Xiomara Rosales at CCRI at (614) 722-6961 or; or Jerry Mendell at (614) 722-5615 or

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Studies and trials target myositis

Several studies for those with polymyositis, dermatomyositis or inclusion-body myositis are being sponsored by the National Institutes of Health (NIH) in Bethesda, Md., as well as medical centers and pharmaceutical companies.

Drugs based on antibodies (immune system proteins) that block inflammation-causing substances are under study in all three types of myositis. In addition, a study of twins or sibling pairs in which only one has myositis, and a comparison of blood components seek to improve understanding of these disorders.

See and enter “myositis” in the search box; or contact the NIH Patient Recruitment and Public Liaison Office at (800) 411-1222 or Some trials are also posted by MDA at

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Unapparent conditions are subject of study

Arizona State University graduate student Aimee Burke, who has a form of muscular dystrophy that’s “unapparent” to most observers, is conducting a study of people who have a medical condition that isn’t obvious to the unknowing observer.

The study will consist of two interviews, subjects will be paid $25 for each. Participants must be at least 20 and have had a diagnosis or symptoms of an unapparent medical condition since age 13 or earlier. Contact Burke at (623) 780-0049 or

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