CelluTarget · Multifocal Motor Neuropathy · Research Frontiers
GeneticsPublished Research

Somatic CAG repeat expansion as a disease-driving process

Overview
Research Summary

Emerging single-cell research shows that the CAG repeat in the HTT gene is not fixed after birth — it can continue to expand over a person's lifetime within specific vulnerable cell types, particularly striatal medium spiny neurons and cholinergic interneurons. This "somatic expansion" appears to be necessary for triggering neuronal dysfunction and is associated with elevated levels of DNA mismatch repair proteins (MSH2, MSH3) that paradoxically promote further expansion rather than correcting it. This reframes HD partly as a DNA repair disorder, not just a static inherited mutation, and has opened a new therapeutic angle: drugs that block the somatic expansion machinery itself, independent of huntingtin-lowering strategies.

Citations
Sources1 source
Peer-Reviewed
Molecular Pathophysiological Mechanisms in Huntington's Disease
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