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preprints:

@melcooperphd.bsky.social - astrocyte networks pubmed.ncbi.nlm.nih.gov/40777296/

@mrodea.bsky.social - single cell analysis & diversity www.biorxiv.org/content/10.1...

@pryprk.bsky.social - XDP www.biorxiv.org/content/10.1..., www.biorxiv.org/content/10.1...

See you in San Diego

🌏 We thank all the amazing clinicians, geneticists, and neuroscientists across continents who contributed to these two studies to better understand and treat this rare disorder.

This work was primarily funded by the Collaborative Center for XDP (CCXDP) and NHGRI’s Center of Excellence in Genomic Science – The Center for Synthetic Regulatory Genomics at NYU Langone Health.

This work represents a close collaboration between the @liddelowsa.bsky.social 🫶 @jefboeke.bsky.social labs at NYU Grossman School of Medicine as a part of The Dark Matter Project @darkmatterproject.bsky.social.

🧬 Dive into the complex genetics of the XDP mice in our companion paper led by Weimin Zhang, Yu (Jeremy) Zhao, Ran Brosh, Jef Boeke, and team:

'Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism'
www.biorxiv.org/content/10.1...

These findings expand the view beyond neurons, revealing glial contributions to XDP and the broader role of retrotransposons in shaping brain health and disease.

🧠 Read the whole story:
'Myelin pathology is a key feature of X-linked Dystonia Parkinsonism' www.biorxiv.org/content/10.1...

There was almost no myelin in specific sub-regions of the XDP brain! (and when there was... it was funkyyy 👀)

But here’s the twist…

🧠 Contrary to the long-standing view of XDP being a medium spiny neuron-specific disorder, we discovered oligodendrocyte dysfunction and widespread myelin disruption as a major and previously unrecognized hallmark of disease pathology — in both mice and human patient brains.

🐭 The motor deficits are wild! Check it out!

Together with @kerrylimberg.bsky.social, @liddelowsa.bsky.social, @jefboeke.bsky.social, & many amazing collaborators, we show that inducing the humanized XDP-TAF1 allele in neural progenitor cells recapitulates key features of the human disease 👉 striatal atrophy and progressive motor decline.

What do you do when there’s no model for a rare disease? YOU BUILD ONE!