Last week at MDA, when we were putting together the final details for the 2013 MDA Scientific Conference, I realized something: I’ve been reporting on MDA’s research program for a very long time — since 1991, to be precise.
Sitting around a table surrounded by iPhones, iPads and laptops, conversing easily with colleagues hundreds of miles away via speaker phone, we began talking about who would write the blogs for this meeting. Someone said Heidi Pottinger, MDA’s director of clinical research who had only been hired by MDA a few days previously, should write a blog from a “newbie’s” perspective (see Giving Our All), while MDA Basic Research Director Paul Muhlrad should write from the research administrator’s viewpoint (see Stirring the Pot). Then someone looked at me and said, “And Maggie can write a blog from an old hand’s perspective.”
I suddenly felt acutely aware of my gray hair and the fact that I was using a pen to take notes on this planning meeting. “Yes,” I said. “This conference needs the perspective of an older person.” So here it is — day one, 2013 conference, my perspective.
Kurt Fischbeck, who’s now chief of the Neurogenetics Branch at the National Institutes of Health, opened the sessions here in D.C. by saying, “This is an exciting time. We’ve finally come full circle in terms of bringing back to patients the possibility of effective treatments based on finding the causes and mechanisms of neuromuscular diseases.”
I thought back to 1991, when I first met Dr. Fischbeck. His hair wasn’t gray then, and neither was mine. In fact, 22 years ago, he was a young researcher at the University of Pennsylvania. The dystrophin gene, which underlies Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), had been identified in 1986, ushering in the age of molecular genetics and changing the way scientists and doctors looked at neuromuscular disease. Instead of describing disorders by their symptoms alone, they began thinking about what was happening at the level of DNA, RNA and proteins in muscle cells.
It was July 4, 1991, when Fischbeck and his colleagues published a paper in the journal Nature that identified a new type of genetic defect as the underlying cause of a disease known as spinal-bulbar muscular atrophy (SBMA, or Kennedy disease). The new type of defect — a “triplet repeat expansion” — would become known the world over the following year, when it was identified as the cause of a more common disorder, type 1 myotonic dystrophy (MMD1). But back then, it was still a novel and mysterious phenomenon.
Since those early days of molecular genetics, it’s become clear that there are a number of ways that DNA can go wrong, and one of them involves DNA sequences that are repeated too many times, as if by a photocopy machine gone rogue. Now we know of the presence of triplet repeat expansions, quadruplet repeat expansions and even hexanucleotide expansions (made of repeating units of six DNA “letters”) that can cause various neuromuscular diseases. And better yet, we have some pretty good ideas of what to do about them and the many disorders caused by other types of genetic errors.
“It’s been 27 years since the Duchenne muscular dystrophy gene was identified,” Fischbeck told the audience. “Now we are fulfilling the promise of that discovery.”
As the conference progressed through its first day, we heard about molecularly based experimental therapies for amyotrophic lateral sclerosis (ALS), DMD, facioscapulohumeral muscular dystrophy (FSHD), MMD and spinal muscular atrophy (SMA), several of which are already in clinical trials and none of which would have been imaginable without the gene identifications of the past two decades.
Genes are frequently referred to as the recipes for proteins. But they’re also the Rosetta stones for genetic diseases. Understand the gene, the protein for which it’s the recipe, what the protein normally does and how it may misbehave or fail to fulfill its duties when it contains an error, and you’re on the path to developing a therapy.
Not only are there clinical trials under way, Fischbeck said, but “we’re now seeing the first glimmers of efficacy popping up like flowers.”
I remember when the first seeds were planted, I thought, and I’m confident I’ll be around when full-fledged therapeutic gardens are in bloom.
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