are inherited diseases. Just from the pattern of transmission within families, it was known they were single gene disorders. There are a lot of different kinds of muscular dystrophy, but the majority of cases are Duchenne Muscular Dystrophy. This is a disease that has received a lot of focus, because it is the most common inherited disease in the world in terms of single gene disorders. It’s more common than cystic fibrosis. More common than hemophilia.
We know now that it’s the largest gene in nature. It’s almost 2.5 million base pairs in size. An enormous gene, almost 10 times bigger than any other gene, so there are a lot of things that can go wrong with this gene. A lot of things can get messed up pretty easily.
X: Given how common it is, and how much attention has been placed on this disease over the years because of Jerry Lewis, why hasn’t there been more progress?
JC: There’s been a tremendous amount of progress, but it’s been a very difficult situation. At the moment, we really don’t have a cure for any genetic diseases. There are some that can be treated with certain drugs. But for the most part, we’re still in a search for cures for a lot of genetic disorders. It’s like cancer, there’s no cure for that.
X: When you say there’s a tremendous amount of progress, it sounds like you’re talking scientifically. But what about progress in terms of life expectancy, quality of life, and patient prognosis for kids born with this?
JC: That has lagged behind a bit. But we are now at the stage where there are a number of viable treatment options starting to move into the clinic. That’s what’s exciting. It’s taken us a while to get there, that’s for sure. The first challenge was just in finding out what the gene was. Interestingly, the gene that causes muscular dystrophy is called the dystrophin gene. It was cloned in 1988. It was really an amazing feat to pull that gene out.
So that set the field in motion. Suddenly we had a gene. But the problem with these genetic diseases is that you have a very fundamental flaw in every cell of the body. How do you go about fixing that? The way to develop therapies depends on the nature of the gene and what it does. In this case, the dystrophin gene makes a protein that is critical to hold muscle cells together. It’s almost like a girder, a 2-by-4, in terms of holding a house together. When those 2-by-4s start falling apart, the whole house collapses. That’s what you have in muscular dystrophy. The muscles cells form normally, but they’re very fragile, and they break down very easily. It turns out this is a defect that really doesn’t appear to be treatable by any kind of conventional drug therapy, like a nutrient or something to augment a particular pathway inside cells. Instead, you’ve got a fundamental structural problem. People are coming to the consensus that the only way to fix that is to replace the structural defect, to rebuild it.
X: So that led people naturally to gene therapy in the 1990s. What happened? Obviously we don’t see any FDA approved gene therapies.
JC: Gene therapy was an enormous challenge, but things are beginning
