Human tissue evidence: TNAP ↑ in Alzheimer’s; GPLD1 ↑ in active elders

1:40:54So in humans they looked at autopsied cortical tissue of older adults with Alzheimer's dementia >> the TAP protein levels are elevated there >> which means there's a lot of these TAP boats that are anchored to the dock >> of the blood brain barrier >> the GLD1 levels were elevated in active healthy elderly humans. So those who are active and healthy >> the Coast Guard was up. So already we're seeing these like large scale correlations, right? And it's hope that this could actually work perhaps in humans. I I thought it was a very cool study because they they did a comprehensive research in mice. Yes. And

1:41:35they and they didn't leave the human the human part >> you know >> because the point is the insights that were derived from the studies in mice are uh in terms of uh autopsy data from past Alzheimer's patients both those who were active and inactive >> basically mimic the levels >> both in this uh the t-ap inhibitors being more present >> uh on on the blood as well as um exercise increasing these this enzyme level. >> Yeah, this one that helps to maintain the structure of the blood vessels and the tight junctions of the blood beam barrier which again seems to be as a

1:42:16competing theory to the amyoid hypothesis a potential uh it's like a lower it's like lower in the um stack >> uh of processes because you want to basically attack a problem as close to the source as possible. >> Exactly. um the amiioid plaque is not the source. >> Yeah, it seems it's not. >> It seems it seems it's not, but this might be >> getting closer >> uh to what it's going on. >> And also just an interesting conceptual way to think about how to look at like neuro uh degenerate neurodeenerative diseases. >> Exactly. As a holistic thing. As a holistic, right? It's like this thing involves the liver, the blood, and the

1:42:57brain. It's the brain is no longer like an island that you have to think about. Right. I mean it's it's I think the future is looking very bright for this particular study. Of course I don't want to do commentators curse but the GPLD1 which is like you know your Coast Guard that thing targets all kinds of boats not just TAP. It's targeting all sorts of GPI anchored proteins >> hundreds of others. So there those could be targets for new therapies, right? Um you could have a antip I mean I anticipate there's going to be a surge in peripheral TENAP inhibitors, not just this >> SBI425. There could be other stuff, >> right? >> So yeah, and I think that's an important point that the the SBI 425 already being

1:43:40an approved drug like is huge because it sort of shows the the drug development >> scaffolding. Yeah. to get to an end result even if you don't use exactly like you you can at least reach like see what the pathway is to success here around how to approach it because you know there's there's the research but then the whole drug discovery process from stage one uh stage one or phase one to phase four quite complex you have early stage drug discovery where they're just trying to figure out like the active ingredients then you give it to the chemists because they have to figure out how do you actually deliver it right >> to the patient is it introvenous is it oral dosing what is the halfife life, all that kind of stuff. Then you get into sort of early pre-clinical trials.

1:44:22>> Yeah. Where it's like, okay, let's make sure it doesn't kill the >> bug, right? Then you get into clinical trials, FDA approval. I mean, it's it is a very complex and long thing >> and this is already halfway through. >> It's already So that's a huge deal. >> Uh fascinating story. >> Yeah, I thought that was very cool actually. >> It's very cool. And I think what's been so interesting in this journey on the show for me, right, having the benefit of just having you able to really again having a first principles general science understanding is not super common unfortunately. Um, and the ability for now like me almost 30 episodes in to be able to make these connections across stories because there's fundamentals about the process

1:45:05of this early stage research or frontier research that track. Yeah. I mean, we talked earlier about the proton piece and how that's like you how measurement not of direct observation, but indirect observation is a concept and it can manifest Yeah. >> at the when you're zooming in really really small or when you're zooming out really really far. I mean, this is a really really cool story and great work. This again was from um UCSF. >> Yeah, UCSF. They do amazing work there. >> Lots of Nobel prizes. >> Oh my god. Fascinating, fascinating story. And again I just want to make a quick sort of caveat here. The point of this show is to talk about breakthrough in frontier research from first

1:45:45principles. There is a large delta or a big gap in between a research paper coming out and it having >> you know over-the-counter or prescription medication available to people. And so just to be very clear about that point >> we very much understand that one there needs to be replication. There's a whole process of implementation. >> There's a lot of stuff that can go wrong in the middle. >> And so the middle is there's a lot there. >> It is it is about kind of the beginning of the story, but it's important just to be clear that that that is that is the case. >> Yeah. >> Um Yeah. >> And so, you know, I know some folks, yeah, this is still early. Yes. >> Yeah. >> But isn't it cool that we figured out

1:46:26this Coast Guard boat docking thing? >> It's the concepts and the ideas are really and understanding how we got there. Yeah, >> is the point. >> Yeah, that's the point. I mean, >> um because there's so many things you can get from this. So, in any event, um >> fantastic. We started with dark galaxies again. We space and then neuroscience, some great rundown stories. I want to do a couple of quick housekeeping notes before we wrap up for the day. Number one is if you are listening to this episode and you've made it all this way, >> congratulations because some of this