MDA's August 1998 Gene Therapy Workshop conveyed the same sense of significance and urgency that I felt at the Association's 1983 Cold Spring Harbor, N.Y., meeting. That historic meeting set the research stage for discovery of the gene whose thousands of variations and defects give rise to all cases of Duchenne and Becker muscular dystrophy (DMD and BMD). The gene was located some three years later by an MDA-supported research team.

The August workshop helped set the clinical stage for MDA-supported investigators to answer a question that goes beyond DMD and BMD and straight to the heart of MDA's mission: Can gene therapy provide therapeutic benefit with virtually any form of MD?

Significantly, gene therapy faces the same hurdles as traditional drug therapy: safety, safety, safety -- and, then, efficacy (effectiveness).

Important contributions to the meeting were made by representatives from the Food and Drug Administration's Center for Biologics Evaluation and Research, or CBER. Taking their recommendations into account, it's clear that, in designing the clinical trials that will ultimately lead to an answer to the question of gene therapy's role in treating MD, it's far better to start modestly with a series of small, focused safety trials than to go directly to the efficacy study.

To maximize the likelihood of developing gene therapy for MD, we must create a series of clinical trial "bridges" that lead us from ignorance to certain knowledge of what viral vector to use, what gene to use, what route of administration to use, what types of patients in which to test each component of the therapy, and so forth, on up to the final bridge.

I thought one MDA-supported researcher captured the spirit and reality of the meeting perfectly when he looked at the CBER representatives and others and said: "Look, tell me what I need to do and I'll do it."

I remember that at the Cold Spring Harbor meeting, there was a pervasive feeling of unreality about the task of gene discovery ahead. No one really knew what to look for or even if the gene underlying DMD made a muscle protein. (At the time, we thought it could have made a nerve, kidney or even liver protein that affected muscle.) The big question we wrestled with then was: How would investigators recognize the gene even if they found it? The answer was: They'll figure it out when they get there!

The spirit of adventure provided, as we now know, a thrilling scientific gallop through a virtually uncharted genetic territory that was led, for the most part, by fearless young MDA-supported investigators embarked on the first big-time scientific journey of their careers. Some were barely out of their training at the time.

The spirit of adventure in gene therapy prevails also, but gene therapy, of necessity, is going to be a slower scientific enterprise than gene discovery. Ultimately, everyone knows what to look for in gene therapy: a safe treatment that improves muscle strength and prolongs life. Nevertheless, gene therapy for any disease is still largely uncharted territory, and MDA investigators must proceed cautiously, albeit unhesitatingly, as they push to the furthest reaches of the medical frontier to be successful.

As we learned at the workshop, in gene therapy, patience and a single-minded course beginning with a series of safety studies is the path to progress, rather than the more "try anything and everything" approach of gene discovery. In other words, the elements for success in gene therapy have some distinct differences from those that were required for our gene discovery effort.

Some of the scientific heads assembled for the gene therapy workshop were graying, in contrast to the young group assembled at the 1983 Cold Spring Harbor meeting. Experience and a reputation for past and present success in the molecular genetics and the physiologic basis of MD are prerequisites for progress on this frontier, and the 1998 research group has those.

Despite all the caveats, there is a strong foundation of knowledge to support a program in gene therapy for MD. Over the past 12 years, since the discovery of the gene underlying DMD, MDA research on the genetic and protein abnormalities of muscular dystrophies has yielded a knowledge base that is both deep and broad. In fact, there appear to be few, if any, significant gaps in our understanding of what's missing, what leads to muscle weakness and what needs to be repaired to provide improved muscle strength in most forms of MD. This knowledge gives us far more confidence about what to look for and how to recognize success when we see it than we could have dreamed of in 1983.

With this workshop, I think it's fair to say that MDA has reached base camp on the mountain of challenges that need to be climbed to achieve a treatment for patients with MD. The exciting news for patients is that every MDA-supported investigator who attended the August workshop started immediately on the climb to the summit.

* * *

Donald S. Wood, Ph.D., was MDA's research director during the 1980s, a period of rapid scientific advances in neuromuscular disorders, and is now MDA's director of science technology. He's president and chief operating officer of the Reproductive Science Center Division of IntegraMed America in Purchase, N.Y.