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Deepak Jha's avatar

Good piece here! Fully agree with the reversal issue vs. slow progression of neurodegeneration.

A key challenge seems to be when to target the glial cells too. Too early/ too late? TREM2 is a good example; too much agonism shuts down downstream signaling (desensitization).

Not to mention, which biomarkers to think about for neuroinflammation or how to consider (or if?) oligodendrocytes.

See recent papers & reviews from Li Huei Tsai et. al for impact of oligos.

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Shireen Rudina's avatar

Super insightful. I really appreciate the point you're making about accessible/known PD biomarkers from I&I. Sure, it's unlikely that these biomarkers serve as efficacy or disease modification markers, and those will continue to be difficult to identify in diseases like AD&PD. But given the uncertain dynamics of brain delivery (at tissue & cell level), having strong confidence PK:PD understanding == better science.

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