Throughout its 50-year history, MDA's research program has faced many challenges. The first was to find out how muscle tissue works and how muscles and nerves work together. In fact, among the earliest questions MDA researchers set about answering was whether muscular dystrophy was caused by a defect in the nerve or in the muscle. (Answer: muscle)

So the 1960s and '70s could be called the "age of physiology" of muscle and nerve.

The 1980s have been called the "genetic age" in MDA's history. For the first time, advances in biomedical technology made possible the rapid identification of disease-related genes and, with those identifications, windows of understanding of disease processes unlike any insights previously imagined. Without the understanding of physiology gleaned in the early years, the leads given researchers by the later gene findings wouldn't have been useful, because they would have lacked a context -- knowledge of the structure and function of normal muscle and nerve.

As the new millennium approaches, MDA is entering a new and exciting period in its history: the treatment era. Thanks to decades of research by MDA grantees throughout the world, we now have in hand the basic elements from which to develop treatments for several forms of muscular dystrophy.

Treatments for other MDA-covered conditions, such as the motor neuron diseases, aren't as clearly visible on the horizon. But, riding the crest of the biomedical revolution, basic research that may lead to effective treatments is progressing more rapidly than ever before.

IN THE BEGINNING

The year was 1950. Almost nothing was known about muscle, let alone muscle disease. Polio had the country's attention, monopolizing the efforts of the best and brightest researchers interested in neuromuscular problems.

That spring, a New York businessman who had muscular dystrophy, a small group of parents of children with the disorder, and Ade Milhorat, a young physician interested in muscle disease, gathered in an apartment in the Bronx and created the Muscular Dystrophy Association of America. Its express purpose was to raise $20,000 a year to fund research toward a cure for muscular dystrophy.

In May, the new association gave $1,500 to Milhorat, who was doing muscle disease research at New York Hospital in Manhattan. By February 1951, it was able to give Milhorat $25,000 more, and MDA's research program was under way.

RESEARCH EXPANDS -- IN-HOUSE AND BEYOND

By 1959, the 9-year-old association had enough funds to open its own research institution, known as the Institute for Muscle Disease, near New York Hospital on Manhattan's upper east side, with Milhorat as its director. The institute became MDA's intramural research program, with MDA grants funding the dozen or more scientists working there at any one time.

Leon I. Charash "We had the whole world as our lab."

But as early as the mid-1950s, MDA also had an extramural research program. By 1957, MDA was funding nearly 100 research projects in 50 medical centers, in addition to projects at its own institute.

The Institute for Muscle Disease flourished from 1959 until the early 1970s, when MDA began to question the need for maintaining its own bricks-and-mortar structure.

"It became apparent that the interest which we had ignited and the information which we had made available about physiology and biochemistry and morphology made it less necessary for us to operate our own institute," says Leon I. Charash, a pediatric neurologist who has headed MDA's Medical Advisory Committee for more than 25 years. By the 1970s, neuromuscular disease research was no longer the stepchild of biomedicine. "We had the whole world as our lab," Charash says.

Today, MDA funds about 325 research projects at a time and allocates some $23 million a year in research grants related to 40 neuromuscular disorders.

DECISIONS, DECISIONS

MDA grants are awarded in what's known as a "peer review" system. Each grant is reviewed as objectively as possible by the candidate's peers, with some oversight by the MDA Research Depart-ment and final approval by MDA's Board of Directors (see "How a Good Idea Becomes an MDA Grant"). The system attempts to balance the judgment of experienced people with the objectivity of numbers and facts.

Grants are awarded on the basis of each application's relevance to MDA's goals of treating or curing our 40 neuromuscular disorders, the strength of the institution in which the research will be conducted and the strength of the scientist who will be conducting it. "Nobody's got a better review system," Charash says. "Other people may also use it, but nobody's come up with a better idea. If there were one, we'd embrace it."

R. Rodney Howell

R. Rodney Howell, a pediatrician and medical geneticist who has headed MDA's Scientific Advisory Committee since 1989, agrees that the system works. Howell has also served on MDA's Medical Advisory Committee and chaired its Task Force on Genetics in the 1980s.

"I was recruited by MDA because I'm a geneticist and there was a perception that genetics was going to really be important," Howell says. "I was the first person with formal training in genetics that came on the committees."

MDA put an enormous amount of effort and funding into finding the Duchenne muscular dystrophy gene in the 1980s, Howell recalls. The committees and the MDA Board "had the courage to put that kind of money in a flier," he says. "This was not a sure thing. Lou Kunkel [whose team found the gene in 1986] was a young guy who was untried. But obviously, he was extraordinary."

"The group, I think, will take chances," Howell says of the committee he chairs. "If something looks like it could be productive or lead to a new thing, although it's not sure, people will buy into that. It's not a bunch of old fogies. I think it's fair and it certainly is an efficient mechanism."

Howell also notes that MDA committee members volunteer their time. Most members of the two advisory committees are current or former MDA grantees, and some are also MDA clinic directors.

"An average person will spend maybe 10 to 12 hours before coming to a committee meeting reading the grants and then writing a critique, and then spend maybe a day or so at the meeting," Howell says. "They volunteer their time because they think it's important to support neuromuscular research."

A BALANCING ACT

MDA has a long tradition of balancing basic science research with treatment-oriented studies, such as clinical trials. As a physician and a geneticist, Howell recognizes the importance of both and the value of finding the right balance at various times.

The dawn of the 21st century may be the right time to push a little extra funding toward treatment strategies for some of MDA's diseases, Howell says, but others, particularly amyotrophic lateral sclerosis, still require a lot more basic science research. To find effective treatments, he says, "you've got to understand how things work. It's essential." 

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