What I’m going to talk about… This is the Sydney Carter lecture. I did know Dr. Carter. I trained at Columbia when he was the chairman. So it has a little special meaning in the sense that he was one of my mentors. So it’s a great privilege giving a talk in his honor. I’m going to talk about how far we’ve come in gene therapy. My first gene therapy experience was more than 20 years ago...
What I’m going to talk about… This is the Sydney Carter lecture. I did know Dr. Carter. I trained at Columbia when he was the chairman. So it has a little special meaning in the sense that he was one of my mentors. So it’s a great privilege giving a talk in his honor. I’m going to talk about how far we’ve come in gene therapy. My first gene therapy experience was more than 20 years ago. And during that time we were relatively naive to the field. The first gene therapy that had ever been approved by the FDA for even the first enrollment of a clinical trial was 1990. And the first major publication was in 1995, on the clinical side of things. And so my experience in 1999 was relatively early. From that point forward for basically the next 20 years, we made gradual step-wise improvement and finally got to, I guess, a major clinical breakthrough. And that was in spinal muscular atrophy.
There were certain things that we changed in order to make that happen. This was, one, a systemic delivery of virus, the highest titer of virus that had ever been given in a clinical trial. And so that was done with a little bit of extra concern and care, and it turned out to be fortunately the right dose. We’ve proven that we had very good, excellent response from the kids and that we had very little toxicity. And so it was, in that sense, a major breakthrough, and we were also targeting infants, and certain things are relevant about that. Spinal muscular atrophy type 1 is a disease that has its onset within the first six months of life. And usually earlier, usually by the first three months, and often shortly after birth it’s recognized.
And treating these very young infants, although it was a matter of concern, and what we found is that these young infants tolerated the virus very well. And we have a lot of comparative data since then, but they did very well, tolerated the dose, and the younger we gave the virus the better the outcome. So that this was, in a sense, rescuing the nerve cells before they underwent degeneration. So, the best outcome we have were the patients who we treated one at four weeks and one at eight weeks. And if we treated them at that earlier time, and they had very few symptoms, they had a very major outcome near normal.
Where we are in clinical practice is very relevant question because the results of this study led to the first systemic gene therapy approval. In that sense, again, it was a major breakthrough because it was the first time now the FDA approved gene therapy given intravenously and at these very high doses.
And, that meant that from that point forward, several things happened. One, very significant was that we were able to have, now in 33 states, newborn screening for SMA. Newborn screening for SMA means that we can reproduce what we did in this first clinical experiment, or first clinical trial. We could treat babies very early. If we could treat them early, we could essentially have very few symptoms once the gene was delivered. And now the gene therapy is approved for clinical use, so that a physician, a neurologist who now recognizes the disease very early or has an alert to it because of a newborn screen in their state, they can treat the babies very early and have similar results to what we have had.
Without being too bold, I would say that what we’re trying to do is to get into the window of time before the spinal motor neurons have been seriously damaged. And if we can get to that point and treat them early, we’re essentially rescuing the neurons from the disease. So we rescue the neurons, and of course we rescue the patient. And I don’t want to say we can cure all of them, but we can certainly make major inroads to producing a normal infant.
