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Alberto J Espay Profile picture
@AlbertoEspay
Apr 27 • 4 tweets • 4 min read Twitter logo Read on Twitter
@MadhavThambiset was the voice of reason at the #AANAM. He delivered a Neurology Year in Review Plenary about the dubious record of the anti-proteinopathy framework inspiring therapies in #Alzheimers, #Parkinsons, and #ALS --Some highlights (1/4) Image
(2/4) Unblinding due to infusion-related reactions or ARIA-H was not accounted for in the sensitivity analysis of the #lecanemab trial. This and other issues have led to an inflated sense of efficacy and underestimated risk for anti-amyloid therapies. ImageImageImage
(3/4) What's the magnitude of brain loss induced by lecanemab over the course of the trial? 3 fewer "teaspoons" of brain lost at the highest ('therapeutic') dose of lecanemab. ImageImage
(4/4) The anti-protein approach is accumulating a similarly dubious record against tau and alpha-synuclein. Time to reconsider this approach. @MadhavThambiset ended with a request for data sharing to all companies involved in these trials. ImageImageImage

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More from @AlbertoEspay

Alberto J Espay Profile picture
Jan 17, 2022
The success of #COVID19 vaccines required heavy investments into #HIV research and the resourcefulness and creativity of many. The 60-year history summarized by @nytimes highlights important lessons. (1/12)

nytimes.com/2022/01/15/hea…
(2/12) 1st milestone: 1960 – “Molecule X” carried copies of DNA segments to ribosomes to make proteins. It is posited to be the "messenger" RNA, or mRNA. Could this molecule be instructed to make tiny pieces of viruses to strengthen the immune system?
(3/12) 2nd milestone: 1960-2005 – Exogenous mRNA was easily degraded by the immune system, treated as an invading pathogen. Native mRNA, it was discovered, is protected with a specific modification. Doing that allowed mRNA delivery without provoking an immune response.
Read 12 tweets
Alberto J Espay Profile picture
Mar 13, 2021
#Donanemab for #Alzheimer, misleadingly spun as positive: “donanemab resulted in a better […] ability to perform activities of daily living than placebo at 76 weeks”. The data suggest otherwise. (1/8)

#EliLilly @NEJM #ADPD2021

nejm.org/doi/full/10.10…
(2/8) First off, donanemab accomplished exactly what it was designed for: At 76 weeks, the reduction in the amyloid plaque level as assessed by florbetapir PET was 85.06 centiloids greater in the donanemab group than in the placebo group (−84.13 vs. 0.93 centiloids)
(3/8) However, the primary outcome, the composite iADRS (range, 0 - 144), showed a difference of only 3.20 points in favor of donanemab. While with a p=0.04, the trial was powered to show a 6-point difference. This goal was not reached, as the authors admit in the discussion.
Read 8 tweets

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