Hopeful Peter Attia Podcast with John Kastelein

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circular
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Hopeful Peter Attia Podcast with John Kastelein

Post by circular »

#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D.

This is such an interesting and hopeful podcast for us. I skipped way ahead past the first part about familial cholesterolemia to hear about Apoe4, and now I'm going to listen again to the entire thing so better grasp it all and can put the ApoE4 information into more context.

The short of it is that the most recent CETP inhibitor being researched is blowing prior versions out of the water in terms of efficacy, and the safety, so far, is still good. They discuss how it may reverse ApoE4's issues with respect to cholesterol, and at least to some extent also inflammation, for a very cheap, low dose pill. I think, although I'm hardly educated enough in this area to have any opinion, they pretty much put to rest the idea that high HDL offsets high LDL. I also now find it hard to believe that ApoE4s need higher LDL to compensate for the dysfunctional way that ApoE4 mismanages LDL metabolism.

I couldn't find this posted yet in the forum, so hopefully it's not a repeat.

Since I don't know this landscape or Peter Attia's perspectives well, I'd love to hear others' comments after listening.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
springmeyer
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Re: Hopeful Peter Attia Podcast with John Kastelein

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I'm new to this forum, but longtime Drive listener. I concur with you that this podcast is an exciting one. So, thanks for posting here. As e3/e4 I'm also interested in others thoughts & take-aways. Upon re-listening to parts of this episode today I was inspired to try to get more up to date news on the CETP inhibitor discussed (obicetrapib). I found the email list https://ir.newamsterdampharma.com/share ... ail-alerts may be a source of upcoming news on the trials happening with it.
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Re: Hopeful Peter Attia Podcast with John Kastelein

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circular wrote: Sat Jul 08, 2023 3:32 pm #255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D....
The short of it is that the most recent CETP inhibitor being researched is blowing prior versions out of the water in terms of efficacy, and the safety, so far, is still good. They discuss how it may reverse ApoE4's issues with respect to cholesterol, and at least to some extent also inflammation, for a very cheap, low dose pill. I think, although I'm hardly educated enough in this area to have any opinion, they pretty much put to rest the idea that high HDL offsets high LDL. I also now find it hard to believe that ApoE4s need higher LDL to compensate for the dysfunctional way that ApoE4 mismanages LDL metabolism.

I couldn't find this posted yet in the forum, so hopefully it's not a repeat.

Since I don't know this landscape or Peter Attia's perspectives well, I'd love to hear others' comments after listening.
springmeyer wrote: Wed Nov 22, 2023 3:19 pm I'm new to this forum, but longtime Drive listener. I concur with you that this podcast is an exciting one. So, thanks for posting here. As e3/e4 I'm also interested in others thoughts & take-aways. Upon re-listening to parts of this episode today I was inspired to try to get more up to date news on the CETP inhibitor discussed (obicetrapib). I found the email list https://ir.newamsterdampharma.com/share ... ail-alerts may be a source of upcoming news on the trials happening with it.
Welcome, springmeyer!

We're glad to have you as a new forum member who found the post from our long-time member "circular". I've "quoted" circular by clicking on the quote icon in the upper right corner of their post, so they get an email notification of your response. It's a handy, if somewhat clunky, way of keeping dialogue going.

I'm way behind on Peter Attia's podcasts, so appreciate you both posting. I found the abstract from an August 2022 article in the respected journal Nature and added some emphasis in boldl:
Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl−1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.
Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial

It seems likely that they will get investor or NIH funding for a large Phase 3 trial based on those results.

Although you found Circ's post apparently easily, here are some other resources you may want to check out:

The Primer is written by Stavia, a practicing M.D. with ApoE4/4. It's a great place to see a wide range of strategies, and in her Appeindix she offers suggestions for biomarkers to track.

Our Stories is a place where you can view the experiences and often the solutions members have shared.

How to get the Most out of the Website offers screenshots and sections on almost any topic you'd be interested in. It's part of our Wiki whose main index page shows the range of interests we have.
And if you're wondering if someone has posted on a topic, try the text box labeled "Search" right under your user name and enter those terms.

Hope you find the forum useful, and share more great research and your own experiences with us!

Nancy
4/4 and still an optimist!
circular
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Re: Hopeful Peter Attia Podcast with John Kastelein

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springmeyer wrote: Wed Nov 22, 2023 3:19 pm I'm new to this forum, but longtime Drive listener. I concur with you that this podcast is an exciting one. So, thanks for posting here. As e3/e4 I'm also interested in others thoughts & take-aways. Upon re-listening to parts of this episode today I was inspired to try to get more up to date news on the CETP inhibitor discussed (obicetrapib). I found the email list https://ir.newamsterdampharma.com/share ... ail-alerts may be a source of upcoming news on the trials happening with it.
Hi Springmeyer, Thanks for finding this. I never did get around to listening again, so I’ve bumped it back up in my pile. I also signed up for news alerts (thanks for the link), and found a 9/21/23 item in their news of interest to us:
NewAmsterdam Pharma Announces Initial Data from Phase 2a Clinical Trial Evaluating Obicetrapib in Patients with Early Alzheimer’s Disease Who Carry an ApoE4 Mutation

-- Observed reductions of 11% and 12% in 24- and 27-hydroxycholesterol in cerebrospinal fluid (“CSF”), respectively, indicating potential improvement of cholesterol metabolism in the brain --
-- Observed 8% increase in Aβ42/40 ratio, a key biomarker of AD risk, suggesting improvement in disease pathology --
ApoE 3/4 > Thanks in advance for any responses made to my posts.
circular
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Re: Hopeful Peter Attia Podcast with John Kastelein

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NF52 wrote: Wed Nov 22, 2023 5:59 pm
Thanks for linking me in Nancy! I’d long since forgotten about this so will make a another attempt to listen again. See my reply to springmeyer above :)
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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