I received a call from MU Professor of Radiology AI-LING LIN, I had left my number.
She was pleased to learn that I have been on Rapamycin for 3 years with no side effects and my personal observations of improved memory.
She is hoping to get 40 healthy participants for her initial study on rapamycin and increased blood flow and afterwards expand the trial. Ultimately focused on prevention and improvement of alzheimer’s in people.
Told her about rapamycin.news
She was unaware of our group. Happy to learn there is a group self experimenting with few negative side effects.
Was pleased to hear her hypothesis of rapamycin seemed on the right track.
I will try to recruit a few participants from our bioscience faculty.
Great to hear of the study. Please keep us in the loop!
Research Description
Dr. Lin is an expert on translational neuroimaging of brain vascular and metabolic function in aging, Alzheimer’s disease, stroke and traumatic brain injury. She developed and applied magnetic resonance imaging and spectroscopy and positron emission tomography to test nutritional and pharmacologic approaches for protecting the brain from aging, traumatic brain injury, and Alzheimer’s disease. She also has applied artificial intelligence to identify markers that are highly predictable for Alzheimer’s disease development and progression and applied gut microbiome analyses to study gut-brain interaction underlying Alzheimer’s disease.
I find this interesting… we obvously need to carefully balance the interest in following the higher dose mice trials that suggest higher dose equate to longer lifespan improvement, and lower doses that may give great immunity enhancement.
I think that this balance is the key issue, and difficult to do given the lack of data and issue that few of us track our immune system function as we ideally would (i.e. via monitoring TREGS , as Dudley Lamming has suggested).
I found this part of this podcast interesting with John Kastelein regarding the potential protection apoA1 has for people with APOE4 Alzheimer’s alleles:
But the CETP inhibitors are interesting as well, and I like what he said earlier(55:00 - 1:08:00), we don’t need PCSK9, nor CETP. According to him CETP deficiency is linked with a longevity, decrease in Alzheimer’s etc. They are studying the possible first working CETP inhibitor.
Obicetrapib
Obicetrapib is a novel, selective CETP inhibitor that potently decreases low-density lipoprotein-cholesterol (LDL-C) as well as increases high-density lipoprotein-cholesterol (HDL-C) and the number of ApoA1-containing lipoproteins.
In July 2021, we reported positive results from a Phase 2 study of oral obicetrapib demonstrating over 50% LDL-lowering as an adjunct to high-intensity statins showing that an oral dose of obicetrapib could potentially address substantial unmet need for patients whose LDL-C levels and cardiovascular risk remain too high despite being treated. Additionally, clinical data from the study showed the genetic mechanism of CETP as an LDL-lowering mechanism, supporting NewAmsterdam’s strategy for developing obicetrapib in metabolic diseases and other major diseases of high unmet need. As of July 2022, NewAmsterdam has initiated all three of its planned phase 3 trials: BROADWAY, BROOKLYN, and PREVAIL.
NewAmsterdam Pharma Announces Initial Data from Phase 2a Clinical Trial Evaluating Obicetrapib in Patients with Early Alzheimer’s Disease Who Carry an ApoE4 Mutation
Not sure… …given that that they have 3-4 large trials in Phase 3 for cardiovascular disease the majority of the company’s valuation is probably from that and less from the small phase 2b with safety/bio markers in ApoE 4.
It depends what you mean by enhancement. According to MB, that aging is a continuation of developmental growth, immune system becomes too efficient, hyper-efficient and the result is sterile inflammation, where immune system attacks the body itself…
I really like MB theory as it really explains most of aging diseases.
As Alzheimers is in its essence also inflammatory makes sense that rapamycin could potentially prevent it, maybe slow it down, but probably won’t cure it.
It seems to be that things around Phase 2a don’t on average have that high valuations, and especially during the last 18 months-ish of the “biotech market correction”.
The market cap is still at the order of magnitude of 1 billion, and given that they only have things in trials and probably have to pay some meaningful royalties and milestone payments to Amgen who I believe they licensed things from the market still seems to think there is some promise.
Phase 2a is a really early measure. As they say on Wikipedia “Determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect”
So - shouldn’t impact valuation much, except on the downside (if it fails).
Blocking Cholesterol Transfer for Alzheimer’s Disease
Fantastic story about CETP inhibition via ApoA1 mechanism on Alzheimer’s disease risk for ApoE4 carriers on NewAmsterdam Pharma’s website:
Alzheimer’s disease is the most prevalent form of dementia and is the fifth leading cause of death in adults aged 65 years and older in the United States. As populations age worldwide, the global burden of dementia including Alzheimer’s disease is expected to triple by 2050.⁷ The global cost of dementia care was estimated to be $1 trillion in 2018 and is expected to increase to roughly $2 trillion by 2030.⁸
Alzheimer’s disease is characterized by:
Extracellular plaques
Amyloid-beta (Aβ) peptides
Intracellular neurofibrillary tangles
Hyperphosphorylated tau and microtubules
Elevated cholesterol levels have been linked to increased risk of Alzheimer’s disease later in life. New biology shows us cholesterol accumulation in the brain precedes disease onset and may cause amyloid protein cleavage leading to Aβ plaque deposition.
Robust genetic and preclinical mechanism. Moreover, recent genetic findings are now elucidating this story. Approximately 60% of Alzheimer’s disease patients carry a defective copy of the gene encoding for apoliprotein E (ApoE). In healthy individuals, the ApoE gene is responsible for regulating excess cholesterol levels and Aβ plaques in the central nervous system (CNS). However, the protein encoded by the ApoE4 variant is significantly hampered in performing this job, and thus these patients are hampered in their ability to clear cholesterol or Aβ plaques effectively, leading to cholesterol and eventually Aβ accumulation in CNS. We now know patients with loss-of-function mutations in the CETP gene are protected from the increased Alzheimer’s disease risk associated with also carrying an ApoE4 mutation, and we are armed with preclinical evidence showing that CETP inhibition can reverse cholesterol accumulation and associated cognitive impairment in mice. Armed with this exciting data, NewAmsterdam has initiated a Phase 1 program to test obicetrapib’s effect on the lipid profile of the brain and its corresponding ability to appropriately clear cholesterol from cells in the brain.
How does CETP inhibition fit into the Alzheimer’s disease story?
People with CETP loss-of-function mutations appear significantly protected from Alzheimer’s disease, especially in patients who carry a copy of the ApoE ε4 gene.
It is believed that increasing ApoA1 levels in the blood increases the amount of ApoA1 that crosses the blood-brain barrier.
ApoA1 in the brain also clears cholesterol via the same mechanism as healthy ApoE proteins.
Obicetrapib has been shown to substantially increase ApoA1 levels in the body, and we are now initiating a proof-of-concept study intended to show this also drives increase in ApoA1 levels in the brain.
We believe that by increasing ApoA1 in the brain via CETP inhibition with obicetrapib we can restore healthy clearance of cholesterol out of the brain so that it can be cleared by the liver.
Researchers have discovered the link between the gut microbiota and Alzheimer’s disease.
For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.
Professor Sandrine Thuret, Professor of Neuroscience at King’s College London and one of the study’s senior authors said, “Alzheimer’s is an insidious condition that there is yet no effective treatment for. This study represents an important step forward in our understanding of the disease, confirming that the make-up of our gut microbiota has a causal role in the development of the disease. This collaborative research has laid the groundwork for future research into this area, and my hope is that it will lead to potential advances in therapeutic interventions.”
The latest Peter Attia podcast with Kaeberlein and Sabatini has an interesting segment on Alzheimer’s. Attia uses rapamycin with some patients with positive blood markers for amyloid. In his patients he sees the blood mekers improve on Rapa.
That’s only suggestive that it’s helpful. But its very promising.ill try to find the timestamp… edit: listen from 1hr13m
