Over the last 47 years, no agency has done more for neuromuscular disease research and patient care than the Muscular Dystrophy Association. In my own experience as a neuromuscular clinician and clinical researcher, the impact of MDA has been critical in three areas: patient services, training of scientists, and research into both the causes of and treatments for neuromuscular disorders.

A BROAD RANGE OF SERVICES

For 10 years it has been my privilege to participate in the MDA clinic at our hospital. It's difficult to overstate the impact of this clinic and its MDA staff on our patients. The MDA clinic guarantees that any patient who has one of the 40 MDA diseases can be seen and followed over the long term, regardless of financial status. Moreover, through this clinic, our patients gain support from a broad community, including other patients, MDA staff and a wide range of other professionals, such as physical and occupational therapists, dietitians, physiatrists, and experts in technologies such as speech augmentation. In the face of disorders that defy curative treatment, this diverse group provides a level of support and encouragement that is an indispensable source of hope for everyone.

ATTRACTING THE BEST AND THE BRIGHTEST

MDA also plays an essential role in the training of scientists. Through its research grants, MDA has funded hundreds of investigators, many in the formative stages of their careers. This funding attracts to the arena of neuromuscular disorders some of the brightest scientists in the country. After receiving an MDA grant early on, many scientists have elected to continue to study neuromuscular diseases as a career-long pursuit. Young scientists just starting their careers often enhance the research directly, through their perspectives on research problems and methods.

MDA research grants were pivotal in my own career planning. An MDA grant in the early 1980s enabled me to begin a study of motor neurons (nerve cells that control muscles) and to acquire new research skills and enough preliminary data to secure longer term, federal funding. Moreover, that early research experience as an MDA grantee convinced me that it would be exciting to make a long-term research commitment to neuromuscular diseases.

BASIC RESEARCH

No MDA activity is more important or has been more fruitful than its support of basic research. In terms of total dollars of research funded, MDA's commitment has been monumental, often rivaling in specific diseases the budget of the federal government. Just as importantly, the MDA research program has been highly strategic; it has focused on particular problems when new methods look particularly promising and it has sustained certain projects when other support was lacking.

This commitment has been essential, for example, in our studies of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). In the mid-1980s, several of us put together a multicenter consortium of investigators to use a new genetic strategy to search for genes that cause ALS. In the first five years, we were told repeatedly by some funding agencies that this project would not succeed. However, MDA believed that this dire disease merited some research risk and helped provide pivotal support for this collaborative effort. As a direct result, the group was able to define first an "address" for an ALS gene and then the defect within the gene itself. This has led to several lines of investigation, including the development of a mouse model of ALS and numerous trials of ALS treatments.

As another example, members of my own laboratory have studied muscle proteins known as sodium channels, which determine the way muscle cells contract to generate force. Defects in these proteins cause a set of muscle diseases that lead to muscle stiffness and temporary paralysis. MDA support of this research program allowed us to expand our studies and to recruit a talented junior scientist to assist the program. Thanks to the MDA funding, that individual has now helped describe specific abnormalities of the affected proteins.

CLINICAL TRIALS, SHARED INFORMATION

In my view, MDA has played two other vital roles in the broad purpose of curing neuromuscular diseases: It has been willing to sponsor treatment trials, and it has been a clearinghouse for information on diseases of muscle and nerve. The emphasis on translating basic discoveries into clinical therapeutics has been a hallmark of the organization.

When MDA researchers working under Louis Kunkel at Boston Children's Hospital discovered the gene defective in Duchenne dystrophy late in 1986, MDA immediately began to sponsor programs designed to treat the disease. After Kunkel's group described the dystrophin protein in 1987 and reported that it's lacking both in Duchenne patients and in a mouse model of that disease, MDA promptly funded studies aimed at replacing dystrophin. Starting in 1989, MDA-funded researchers, including our group, tested the idea that direct implantation of muscle cells into Duchenne patients might replace the missing protein and improve strength. (This has been called myoblast transfer and, although the early human trials were not successful, MDA has continued to support studies in animals to improve the procedure.) In 1991, MDA began an ambitious program testing the possibility that modified viruses might be used to deliver the dystrophin gene. This "gene therapy" effort continues and is a major part of MDA's research thrust in Duchenne.

It's also a tribute to MDA that many of the lessons learned in these programs will illuminate and benefit other areas in medicine.

MDA has also been a catalytic force in research by fostering better communication within the research community. This role is fulfilled in many ways. At frequent intervals, MDA sponsors major symposia reviewing research progress in different diseases. These bring together basic scientists and clinicians from around the world to share new results and ideas, typically in settings which promote candid, constructive exchanges of information. (It was an exciting, MDA-sponsored, two-day conference on cell therapy in muscle in 1989 that provided the basis for our initial work on myoblast implantation.)

MDA has also provided major funding for international symposia on muscle disorders. At one of these, in Munich in 1990, we established a collaboration with another laboratory that led to developing new genetic markers on chromosome 21 around the area of the ALS gene.

MDA has also helped enormously by holding frequent, small workshops for specific groups of investigators studying individual diseases. Through a series of these workshops, our ALS group has been able regularly to review our combined data and to plan new lines of experiments.

For those of us who see neuromuscular patients and struggle to understand and ultimately treat their disorders, MDA is invaluable. Its patient services are the cornerstone of our clinical activities. Its commitment to research is incandescent.

Ten years ago, we didn't know the primary cause of any of the MDA diseases. For the majority of them, the cause is now identified. There is no doubt that the next 10 years will witness equally exhilarating progress and that, in all likelihood, the MDA research program will produce entirely new, effective forms of treatment for many of these disorders.

Dr. Robert H. Brown Jr. is an associate professor of neurology at Harvard University Medical School in Boston. He co-directs the MDA clinic at Massachusetts General Hospital and directs the MDA /ALS Center at that institution. He's a long-time MDA research grantee in ALS, Duchenne dystrophy and other neuromuscular disorders, and serves on MDA's Medical Advisory Committee.