to be effective when delivered intravenously. They may be able to modify it in pill form. They appear to be effective at getting out of the bloodstream, and penetrating into muscle cells. That was a huge advance.
X: Can you expand a bit on the recent data from AVI? Why do you consider that promising?
JC: It’s just that they had been able to see an effect in humans that mirrored what they had seen in animals. So often with development of therapeutics, you get promising results in a mouse, and then you take it into the clinic and it doesn’t work. What they did was a simple safety study, with an intramuscular injection. What they were able to show, at the injection site, is that they saw restoration of the dystrophin protein coming back on muscle cells. What that says is that the mechanism of action in humans mirrors what we saw in the animal models. That’s a critical step to take, to then go on to develop a delivery mode for whole-body treatment.
X: So they have to go from a single-injection site to a drug that is available throughout the whole body. That’s a big step. Is there anybody further along in trials?
JC: Not with that technology. There is another group doing a slightly different version of the trial. The AVI approach is using morpholinos [a modified antisense oligonucleotide], which I think is going to be the molecule of choice, because they have the longest half-life. Another group [Netherlands-based Prosensa] is using more raw, unprocessed antisense oligonucleotide, and they are a little bit ahead in clinical trials. They published their Phase I trial a year ago, and are gearing up to start their Phase II trial.
They had a publication in the New England Journal of Medicine that was similarly encouraging. They showed they could restore dystrophin.
I have my bias, because the primary approach we work on in this lab is viral vector based gene therapy. But we’re also doing some stem cell work. But in our hands, we can take a mouse model for Duchenne Muscular Dystrophy and give a single injection of our virus, and the mouse is cured for the rest of his life. That’s it, one injection that takes 30 seconds to do, and we have a lifelong cure. We have a dramatic expansion of lifespan in these mice, we treat every single muscle in the body. We completely halt the development of dystrophy, we bring back the sense of normal strength in those mice. Nobody using morpholinos or oligonucleotides has shown anything more than a couple of months of effect. It wears off. They haven’t been able to extend lifespan. They haven’t been able to treat the heart. None of those drugs get into the heart. Our vectors get into the heart very easily.
X: Has anyone shown any commercial interest in taking forward the gene therapy approach?
JC: There is one company in North Carolina (Asklepios) that was formed by a laboratory that’s doing very similar things to what we’re doing here. They’re a competitor of ours, and they raised
