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Could This Be the First Parkinson's Disease Modifier? · CareTalk: Healthcare. Unfiltered.

• 0:08
  David: A Parkinson's patients and families are well aware of the limitations of current treatments.
• 0:13
  David: It's really just about managing symptoms, at least what I've seen, uh, thus far.
• 0:18
  David: And my belief is that gains approach is pretty different.
• 0:21
  David: Um, can you explain what it is that the drug does and why you think it could be the first disease modifying therapy for Parkinson's?
• 0:29
  Gene: Yeah.
• 0:30
  Gene: So, um, you're absolutely right.
• 0:31
  Gene: For decades now, the only, um, relief we've been able to offer to Parkinson's patients has been, uh, some kind of mask over their symptoms, and that wears off over time and the disease, the pathology, and the disease progresses.
• 0:44
  Gene: So what do you do to address that?
• 0:46
  Gene: What do you get to the underlying biology and you try to correct on a molecular level?
• 0:50
  Gene: What's happening, um, to create these symptoms.
• 0:53
  Gene: And we believe that GT 0 2 2 8 7 is going to be among the first, if not the first, uh, disease modifying, uh, therapeutics based on the data that we've seen so far, the preclinical, um, efficacy that we've seen of the preclinical mechanism, uh, that we've seen this drug, um, uh, uh, uh, work through.
• 1:11
  Gene: Um, suggest disease modification at every level.
• 1:14
  Gene: We have tested it at, um, including what we think is, you know, the phase one B in patients now Parkinson's, where we're seeing biomarker evidence.
• 1:23
  Gene: Um, these are the actual bio biological indicators.
• 1:27
  Gene: Of how the disease is, um, is progressing.
• 1:30
  Gene: We're seeing what we believe, uh, is some real impact there, uh, in the presence of GT 0 2 2 8 7.
• 1:36
  Gene: Um, and we believe it is being, it's linking to a clinical benefit early days in this study still, and we have low numbers of patients, but the signals are impossible to.
• 1:47
  Gene: Um, and that's what's really exciting about what Gains doing now.
• 1:51
  Gene: Um, we've just recently presented data at a, at a, a global conference in Copenhagen called the A DPD conference.
• 1:58
  Gene: Data was very well received there, and we think we've given, um, the field a lot to think about now in terms of how, what we're seeing in the biomarkers, and hopefully they're gonna do work that's similar to ours and, and help us understand it better based on, you know, the, the, the, uh, the drug development that they're doing.
• 2:15
  David: Great.
• 2:15
  David: So let's go, just go a little bit, uh, deeper in terms of how things work.
• 2:20
  David: And I'm just, uh, not an expert, but just looking at your materials and seeing that it appears that, uh, your drug is targeting a misfolded enzyme and works through an, I think, pronounced allosteric mechanism.
• 2:32
  David: It's not binding to the active site.
• 2:34
  David: Why, uh, does that matter?
• 2:36
  David: And what makes this kind of allosteric modulation potentially a better approach.
• 2:41
  David: So not just you're getting the clinical evidence, but you know what, why is it that you think that may be an underlying better way to go?
• 2:48
  Gene: Yeah.
• 2:48
  Gene: And that question is essential to what we're trying to achieve here too.
• 2:51
  Gene: So the allosteric binding, we're, that's a, what does that mean?
• 2:55
  Gene: So there's ways to, there's different ways to bind a, a target protein or enzyme.
• 2:59
  Gene: Um, typically if you bind it at the active site, um, you're looking to probably try to inhibit that particular enzyme.
• 3:05
  Gene: Maybe it's overactive or it's have to, it's, it's, it's, it's misfunctioning in a, in a hyperactivity way, right?
• 3:11
  Gene: So you wanna, you wanna, you wanna, you wanna, uh, disable some of that enzyme.
• 3:16
  Gene: Sometimes you can bind to the active site and actually enhance the activity too.
• 3:19
  Gene: It all depends on the binding kinetics and what's happening in that, that particular area of the molecule and what, what, how you're impacting it.
• 3:26
  Gene: Uh, based on that binding.
• 3:27
  Gene: Now what we do is we move further, mostly further away from the active site.
• 3:32
  Gene: We're looking to stabilize the enzyme.
• 3:34
  Gene: So if you remember from high school biology, the lock and key mechanism for proteins and enzymes, their, their, their, their function is determined mainly by their conformational shape.
• 3:42
  Gene: So if that gets disrupted either through genetic mutation or some sort of post, you know, some, some sort of post-translational modifications to the protein.
• 3:49
  Gene: So after it's transcribed and it's sitting in the cell, you know, if something comes along and disrupts it.
• 3:54
  Gene: Um, so what can you do in order to preserve.
• 3:58
  Gene: The function of an enzyme, um, uh, that might be, you know, genetically malformed or under assault some other way.
• 4:04
  Gene: Well, so we bind to an allosteric pocket on this enzyme, stabilize the conformational shape of the protein, and chaperone that that enzyme through its tropic pattern in the cell and the particular target.
• 4:17
  Gene: GT 0 2 2 87 is an enzyme called glucose cerebro.
• 4:21
  Gene: It's a mouthful.
• 4:22
  Gene: We shorten it to G case.
• 4:23
  Gene: G case is a very well-defined, very fairly well understood enzyme.
• 4:29
  Gene: Um, that is prominent in the pathophysiology of Gaucher in the periphery mainly.
• 4:33
  Gene: So that's another disease where, where this particular enzyme is not working properly.
• 4:38
  Gene: Um, but in Parkinson's patients it also plays a role too, particularly if you have.
• 4:43
  Gene: Uh, what's called the GBA one mutation and the gene that encodes.
• 4:48
  Gene: For glucose cerebritis, if that, if you're carrying a, um, uh, a mutation in that gene, uh, your enzyme function is going to be naturally lower than a normal individual or a person who has, uh, you know, uh, normal levels of G case activity.
• 5:01
  Gene: So we're trying to enhance that, that protein activity, enzymatic activity in Parkinson's patients, because that enzyme is responsible for clearing out toxic substrates that build up in the cell and create those symptoms over time.