MDA PHYSICIANS REVIEW
PROGRESS IN FOUR DISEASES

TUCSON, Ariz., Nov. 12, 2002 — Some 180 physicians, scientists and other professionals associated with the Muscular Dystrophy Association gathered here last week for a stellar lineup of updates on medical care and scientific progress in neuromuscular diseases.

The National MDA Clinic Directors Conference, held in the city of MDA’s national headquarters, offered medical professionals a unique opportunity to exchange information and plan for the future.

MDA President & CEO Robert Ross said, “We're gratified to see the enormous energy that was displayed at this gathering of directors in MDA’s nationwide clinic network. Therapies for four major disease groups in MDA’s program were the main focus of the meeting because they’re moving quickly from the laboratory to the clinic. There was a lot of excitement about those developments."

LOU GEHRIG’S DISEASE
Conferees discussed the view of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) as a group of diseases rather than as one disease. Dividing the disease into subtypes will help physicians better understand the course of ALS and give individual patients a more accurate prediction of the pace of their disease.

Only one drug, riluzole, is on the market for ALS. It offers a modest increase in survival for those with this devastating disease, which strikes adults in the prime of life and is usually fatal in three to five years.

Current trials of at least seven potential new treatments are based on new screening techniques in mice with a disease similar to human ALS. Trials combining some of the most promising substances with riluzole are being planned.

Physicians who treat ALS emphasized the importance of helping patients with their respiratory and nutritional needs, for improving quality of life and survival.

SPINAL MUSCULAR ATROPHY
In spinal muscular atrophy, another disease group covered by MDA, significant advances have been made in improving molecular diagnosis and, even more exciting, in planning for therapeutic trials of promising compounds.

SMA, when it begins in infancy, is often fatal. Forms with onset later in childhood or adulthood allow for much longer survival and varying degrees of function.

Research, much of it funded by MDA, has revealed that increasing the activity of a gene in people who have SMA may treat or even cure the disease. Safe and effective compounds that may do this are on the drawing board.

Scientists are also exploring gene transfer (injection of a functional gene to perform the work of a faulty one, also called gene therapy) as a possible therapeutic avenue in SMA. Experiments in mice have shown promise, but much work remains before human trials can take place.

DUCHENNE MUSCULAR DYSTROPHY
In Duchenne muscular dystrophy, a devastating muscle disease of boys that’s usually fatal by young adulthood, scientists are encouraged about results of gene transfer trials in mice with the disease.

Conference attendees heard presentations from scientists who are working with miniaturized versions of the large gene for dystrophin, a muscle protein that’s missing in DMD. A gene delivery system that appears safe and effective has been developed to transfer the gene into muscle cells, and the miniaturized gene itself appears to be therapeutic, at least in mice.

Clinical trials are planned for the near future, as soon as regulatory requirements can be satisfied and the gene transfer vehicle can be manufactured for human use.

LIMB-GIRDLE MUSCULAR DYSTROPHY
At least a dozen different genes can, when flawed, lead to forms of limb-girdle muscular dystrophy (LGMD). LGMD causes muscle wasting, mostly in the hip and shoulder areas, but it also sometimes affects the heart and respiratory muscles.

Finding out how each gene flaw leads to the disease is an important part of MDA-supported research that will likely lead to targets for therapeutic drug development.

Details about a brief 1999 gene therapy trial in LGMD were presented at the meeting. In one participant, an injected muscle showed a small amount of protein production from the transferred gene, but the other participant’s injected muscle showed no production. In hindsight, the muscle that was chosen may not have been optimal for this early experiment, the investigators noted.

They plan to restart the trial as soon as possible, using a different test muscle. Meeting regulatory requirements and developing a gene transfer vehicle for the trial are among MDA’s top priorities.

GENETIC TESTING
The conferees also learned that MDA is initiating a program whereby Athena Diagnostics will set up customized agreements with each MDA clinic for wide range of diagnostic testing services offered by Athena. DNA testing for genetic diseases has become a crucial part of patient care and family planning for those MDA serves.

An additional highlight of the meeting was the announcement that the Association is developing a password-protected Web site uniquely suited for physicians and other neuromuscular disease professionals to exchange information in an even more efficient manner than has been possible until now.

MDA (www.mda.org) is a voluntary health agency working to defeat more than 40 neuromuscular diseases. The Association supports some 230 clinics and 29 MDA/ALS centers in the United States and Puerto Rico, as well as some 400 research projects worldwide.