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Galen Wright

@galenwright.bsky.social

1.1K followers 646 following 8 posts

🇿🇦 🇨🇦 Assistant Professor University of Manitoba | Canada Research Chair in Neurogenomics | precision medicine | neurological disorders | DNA repair in the brain

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Galen Wright @galenwright.bsky.social · 22/01/2025

Aggregating total evidence revealed that the mismatch repair gene PMS1 ranked favourably across all the features that we studied, while HTT (where therapeutic knockdown is being extensively studied) appears to be a theoretically riskier drug target

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Galen Wright @galenwright.bsky.social · 22/01/2025

Although all have human genetic evidence (associated with ⬆️ clinical trial success) for modifying HD AOO, we studied new genetic features associated with clinical trial failure (genetic constraint, interactions & broad expression). HTT performed poorly www.nature.com/articles/s41...

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Galen Wright @galenwright.bsky.social · 22/01/2025

We assessed which human traits and diseases are associated with HD modifiers. Some DNA repair genes are linked to cancer, potentially increasing Tx risk. Beyond DDR, we demonstrated that certain 'toxicity driver' HD modifiers were connected to pathological aggregates in GWAS

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Galen Wright @galenwright.bsky.social · 22/01/2025

First, we wanted to emphasize the cross-repeat expansion disorder relevance of HD genetic modifiers. Top HD AOO GWAS variants show similar effect sizes in another RED XDP (CCCTCT repeat). Developing a successful HD modifier therapeutic may also be relevant for other REDs (n=>60)

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Galen Wright @galenwright.bsky.social · 22/01/2025

GWAS has made progress in identifying genetic factors (e.g., MMR/DDR 💣🧬genes) contributing to the age of onset (AOO) in HD outside of CAG repeat length. Our study used diverse human genomic information to prioritize these genes for therapeutic research

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Galen Wright @galenwright.bsky.social · 22/01/2025

I am excited to use my first post on this platform to share the results of a new study from the lab! Genomic characterization of Huntington’s disease genetic modifiers informs drug target tractability Available in Brain Communications academic.oup.com/braincomms/a...

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