UC San Diego Clinical Trial To Assess Safety, Effectiveness Of Alzheimer's Treatment

Speaker 1: 00:00 There is promising news in the effort to treat Alzheimer's disease researchers at the university of California, San Diego school of medicine launched a first in human clinical trial. They are looking at the safety and efficacy of a gene therapy that delivers a key protein into the brains of people with Alzheimer's disease or mild cognitive impairment. The principal investigator of the clinical trial is Dr. Mark [inaudible]. He is a professor of neuroscience and director of the translational neuroscience Institute at UC San Diego health. And he joins me now, Dr. [inaudible] welcome. Speaker 2: 00:36 Thank you very much. It's nice to be here. Speaker 1: 00:39 This clinical trial is going to be very interesting to a lot of people. Can you describe what it is? You're testing? Speaker 2: 00:46 Yeah, we're using a gene therapy to introduce a protein into the brain that in animal studies prevents the death of cells in the brain and promotes the formation of new connections between cells. So in animals, when we do this, we see a reduction in loss of cells, and we actually see an improvement in memory function. The question we're testing the trial is whether these benefits will be observed in people who have Alzheimer's disease. And gene therapy in the last few years has achieved just remarkable breakthroughs in at least one neurological disorder called spinal muscular atrophy. In that case, a replacement gene for a deficient gene was introduced into children who would otherwise die by the age of two. All of the children that were treated are still alive, and that's simply by taking a gene and the viruses we use to introduce a new gene into the body of those children. We're trying to do something analogous in this study, which is to introduce a gene that's normally present in the brain, but making much more of this gene for a growth factor called BDNF and hoping to over produce it in a region of the brain where cells are dying and prevent their death. And the same approach in animals literally builds new connections. So we would like to try this in Alzheimer's disease and mild cognitive impairment and see if it's beneficial. Speaker 1: 02:12 And do you know if there are other clinical trials for the treatment of Alzheimer's, Speaker 2: 02:17 There were lots of clinical trials for the treatment of Alzheimer's disease and that's an issue we face in recruiting patients. Um, the reason we're excited by this one is that this is the only potential therapy to our knowledge that can literally recover memory. The other clinical trials are trying to slow cell degeneration, and we too are trying to do that. But in addition, unlike these other approaches, this growth factor gene that we are delivering literally builds new connections and on that basis and restore memory in animals. So this is unprecedented in the realm of Alzheimer's disease therapeutics. Speaker 1: 02:55 That's amazing. And you mentioned BDNF, it's something we've all got in our brains, but can you tell me what happens when we don't have enough of it Speaker 2: 03:02 When we don't have enough of it, then cells degenerate and sometimes die. So, you know, an Alzheimer's disease, there is a deficiency of this normal protein called BDNF in the region of the brain that undergoes degeneration earliest in Alzheimer's disease. That's in the memory circuitry called the hippocampus. And, um, it, we don't think that Alzheimer's disease is caused by the loss of BD enough. We think the loss of BD enough in Alzheimer's disease is a consequence of amyloid what's called pathology. So these other things, the amyloid, the towel and aging are responsible collectively for causing Alzheimer's disease. As a consequence of that, these levels of this growth factor decline. And again, we're replacing the growth factor, not just to normal levels, but to extra high levels and in an effort to really combat this degeneration, Speaker 1: 03:55 You know, it takes quite a while to get to the point of human trials. I imagine. Um, how long have you been studying this particular therapy? Speaker 2: 04:04 We've been studying this for about 15 years? Gene therapy is a, is a, um, important undertaking. We are genetically engineering cells in the brain. We are changing the cells, the brain. So to be able to bring that to people, you really have to be very careful. You have to do enough, uh, studies in animals to really show that it's a compelling enough effect to merit bringing it to people. And you really have to show that it's safe. And so we did a number of studies. We started with amyloid mice. Then we went to rats and agent rats. And then we even took this through monkeys and found that it continued to have these, these effects that were beneficial and that it was safe. You know, you might ask what are the potential risks of this? And the largest risks that we identified in the animal studies was the risk of seizures. If we introduced this into the wrong place in the brain. But interestingly, those seizures are a reflection of activating brain circuits. That's something that we want. And if we can accurately deliver this to the part of the brain where the cells are degenerating, we don't see seizures. Speaker 1: 05:09 Um, and this trial is in phase one right now. Where do you go from here? What's next? Speaker 2: 05:14 Well, we'll see if in our first patients, it is safe. We can see whether it will actually improve memory. Um, and if it is safe, uh, then we'll move on to larger phase two clinical trials. So, uh, we are recruiting patients for this trial now, hopefully from the local San Diego region. And if we see good evidence of safety and maybe some evidence of effectiveness, then we'll move into larger clinical trials. Speaker 1: 05:39 If all goes well, what kind of a timeline are we on? What about two to three years? Okay. I've been speaking with Dr. Mark [inaudible], professor of neuroscience and director of the translational neuroscience Institute at UC San Diego health. Dr. [inaudible]. Thank you so much for joining us. Speaker 2: 05:57 Thank you.