Short stuff

Most of my posts are long — maybe too long. The charitable explanation is that I can’t resist my instincts as a professor to explain stuff so my learners can understand it. The less charitable explanation is that I’m just a windbag. So here are a bunch of very brief items of news, ideas and opinion about PSP and CBD in the style of Twitter. In fact, I’ll even limit my character count to 280, including spaces. Here goes.

A group in Bologna did skin biopsies to look for a phosphorylated form of α-synuclein in PD, PSP or CBD, and controls – 26 subjects in each group. They found it in all 26 with PD, in no controls, and in 24 with PSP/CBD. (The other two had PD-like features.) Now: how about MSA?

You’ve noticed that CurePSP’s publicity materials call PSP, CBD and MSA “prime of life” diseases because those conditions’ usual decades, the 50s, 60s and 70s, are when life can otherwise be lived to the fullest. Do you agree? Let me know.

A group called the PSP Research Roundtable was formed in 2017 to help speed the process of testing promising drugs. It’s run by CurePSP and has membership from academia, the FDA, the NIH, drug companies, biotech, philanthropy and patient advocacy groups.

Transposon Therapeutics has started a Phase 2 trial of TPN-101 in PSP at private clinical trial sites in Boca Raton, FL and Farmington Hills, MI. Like many available HIV drugs, TPN-101 inhibits the enzyme reverse transcriptase, but otherwise, details are sparse.

About the mechanism of action of TPN-101: I can tell you that another reverse transcriptase inhibitor routinely used for HIV called efavirenz (trade names Sustiva and Stocrin) reduces tau aggregation. CurePSP is currently supporting a study of it in a mouse tauopathy model in The Netherlands.

Enough for now. No windbag, I.

2 thoughts on “Short stuff

  1. Your post encouraged me to look up Dr. Rik van der Kant’s CV, and found a recent review in Nature Reviews NeuroScience, 2020,21,1, 21-35. They discuss the various proposed amyloid independent mechanisms for AD. Figure 3 outlines three of the proposed triggers for tau aggregation: Endocytosis, Cholesterol, and Immunological/Microglia. In the cholesterol scheme they highlight three druggable enzymes (HMGCoA, ACAT, and 24-OH Cholesterol Hydroxylase). The 3rd is a brain specific Cytochrome P450 (CYP46A1). Apparently, this P450 is activated by efavirenz, which is independent from its known activity as a reverse transcriptase inhibitor. I gather that the proposed MOA for the inhibition of tau aggregation is based on shuttling cholesterol away from ACAT which makes cholesterol fatty esters, thought to be triggers for tau aggregation. Anyway, TPN-101 which Transposon is currently is testing I believe was recently licensed from Oncolys, was originally named Censavudine (discovered at Yale in 2006), & also in development for HIV by Bristol Myers Squibb.
    So, my thanks to CurePSP for sponsoring the research in the Netherlands, and I remain hopeful for new treatments for PSP!

    • Thank you, Dr. Swanson, for that explanation. As you know, but other readers may not, repurposed drugs are often a drug developer’s best friends these days, as their safety and pharmacokinetic profiles are already known. Screening procedures for libraries of approved drugs are already in routine use by drug developers. As our tauopathy lab models improve, it’s a good bet that one of those, coupled with a high-throughput screen of approved drugs, could give us the answer.

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