I've finally digested the data that Uniqure presented on AMT-130, their gene therapy for Huntington's disease, which just announced a positive trial readout with 75% slowing of disease progression. Here is a blog post with my take on the announcement:

Registration is now open for Keystone Nucleic Acid Therapeutics & Targeted Delivery in Banff Mar 9-12 2026, I'm co-organizing with a few of my favorite people - please join us! https://t.co/wxq4IXKy97

Here is Sonia with our semi-annual newsletter https://t.co/dEz30CBVGC Donations will be matched 1:1 through end of June!

New @biorxivpreprint from us + Ionis: how ASO activity is distributed across cell types in deep brain regions of NHP https://t.co/cnZNCaHDiV The take-home message in one figure👇

We developed a new siRNA drug candidate for prion disease, a @broadinstitute / @RTI_UMassChan collaboration. We now have an open IND meaning FDA has given us permission to start first-in-human trials. Work remains before trials can launch. The full update:

New on @biorxivpreprint: AAV-vectored zinc finger repressors against brain PrP. Discovery of potent ZFs to the PrP promoter, efficacy in a disease model, distribution of pharmacologic activity at the single-cell level & delivery to NHP in a novel capsid.

A new gene-editing treatment extends lifespan by about 50 percent in a mouse model of prion disease and could lead to a preventative, one-time treatment for the deadly neurodegenerative disorder. https://t.co/s0tX7gbC4g

Today we report in @NatureMedicine the development of a base editing strategy for prion disease, currently a fatal and rapidly progressing neurogenerative condition with no effective treatment. @PrionAlliance @DevermanLab (1/13) https://t.co/jYVDj7JPBZ

As of this morning, the Ionis clinical trial of PrP-lowering ASO ION717 is fully enrolled at N=56 participants, and not taking any more. They've added an Open Label Extension for patients in the trial to receive drug for 70 additional weeks. New post: https://t.co/GDoKtNVF6a

Researchers have long speculated whether VPSPr — a rare prion disease subtype — might be genetic but caused by something other than PrP protein-coding variants. We sequenced 67 cases, and found nothing. It's probably genuinely a sporadic disease

Today we introduce a new drug candidate for prion disease: a PrP-lowering divalent siRNA. A 4-year collaboration with @RTI_UMassChan enabled by @NINDSfunding IGNITE & URGenT mechanisms. https://t.co/Z10daPZGEw Our hope is to advance this to the clinic, wish us luck!

Sonia with our end-of-year update on developing a therapy for prion disease. Two new efforts from our lab: CHARM and divalent siRNA, and an update on the Ionis clinical trial. Support our work with a 1:1 matched donation through end of 2024. https://t.co/KfMVJmFpXy

Fantastic 1-day symposium on AAV re-dosing & treatment in seropositive patients last week at Broad. Here are my notes:

We just had a fantastic primer on AAV from @DevermanLab's Ken Chan to close out the week

Ionis Pharmaceuticals' PrProfile clinical trial of ION717, a PrP-lowering ASO in prion disease, has resumed recruitment:

Honored to be a part of this collaboration and work with such an incredible team! Check out the fantastic CHARM paper led by @EdwinNNeumann and @TessaBertozzi, as well as Eric’s awesome break down both here and on the @cureffi blog!

We believe this will forge a path to a much-needed prion disease treatment, and we think CHARM could potentially be applied to other neurodegenerative diseases. Please also check out this excellent perspective piece by @mn_whittaker and @kiranmusunuru! https://t.co/SpzJ8PdWQf

Working with @FionaSerack & co. in the lab of prion experts Sonia Vallabh and Eric Minikel @cureffi, along with AAV expert Ben Deverman @DevermanLab & co., we demonstrate that CHARM can potently repress the prion protein throughout the mouse brain.

Sharing my first 1st author paper, now published in Science! For my PhD I engineered CHARM, a compact, enzyme-free epigenetic editor which can be delivered via AAV vector to reach the brain. This work was done in @JswLab with @TessaBertozzi and @ElaineWu0 https://t.co/DrV4EGe92z

Still a long road to clinical application. But with the advent of AAVs to bind human receptors - see recent breakthrough from @DevermanLab https://t.co/oCVHkcBl09 - we can now imagine this one day being a therapy for prion disease.