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AAN 2022 | Targets in DNA repair machinery for the treatment of Huntington’s disease

Jee Bang, MD, Johns Hopkins University School of Medicine, Baltimore, MD, discusses the role of DNA repair in Huntington’s disease. GWAS studies in Huntington’s disease have identified several loci which contain genes involved in somatic expansion; many of the loci are involved in DNA repair and more specifically in mismatch repair. These loci offer new therapeutic potential as inactivating the mismatch repair pathway genes has been shown to reduce somatic expansion. For example, knock-out of MSH3 can reduce CAG expansion. Based on this data, a Phase I study is being planned to study an antisense oligonucleotide which targets MSH3. In addition to this, there has also been data which has revealed high selectively for somatic expansion in medium spiny neurons. This interview took place at the American Academy of Neurology 2022 Congress in Seattle, WA.