Nature Communications (Mar 2022)
An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion
- Caroline Gubser Keller,
- Youngah Shin,
- Alex Mas Monteys,
- Nicole Renaud,
- Martin Beibel,
- Natalia Teider,
- Thomas Peters,
- Thomas Faller,
- Sophie St-Cyr,
- Judith Knehr,
- Guglielmo Roma,
- Alejandro Reyes,
- Marc Hild,
- Dmitriy Lukashev,
- Diethilde Theil,
- Natalie Dales,
- Jang-Ho Cha,
- Beth Borowsky,
- Ricardo Dolmetsch,
- Beverly L. Davidson,
- Rajeev Sivasankaran
Affiliations
- Caroline Gubser Keller
- Novartis Institutes for Biomedical Research
- Youngah Shin
- Novartis Institutes for Biomedical Research
- Alex Mas Monteys
- The Raymond G Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia
- Nicole Renaud
- Novartis Institutes for Biomedical Research
- Martin Beibel
- Novartis Institutes for Biomedical Research
- Natalia Teider
- Novartis Institutes for Biomedical Research
- Thomas Peters
- Novartis Institutes for Biomedical Research
- Thomas Faller
- Novartis Institutes for Biomedical Research
- Sophie St-Cyr
- The Raymond G Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia
- Judith Knehr
- Novartis Institutes for Biomedical Research
- Guglielmo Roma
- Novartis Institutes for Biomedical Research
- Alejandro Reyes
- Novartis Institutes for Biomedical Research
- Marc Hild
- Novartis Institutes for Biomedical Research
- Dmitriy Lukashev
- Novartis Institutes for Biomedical Research
- Diethilde Theil
- Novartis Institutes for Biomedical Research
- Natalie Dales
- Novartis Institutes for Biomedical Research
- Jang-Ho Cha
- Novartis Institutes for Biomedical Research
- Beth Borowsky
- Novartis Pharmaceuticals
- Ricardo Dolmetsch
- Novartis Institutes for Biomedical Research
- Beverly L. Davidson
- The Raymond G Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia
- Rajeev Sivasankaran
- Novartis Institutes for Biomedical Research
- DOI
- https://doi.org/10.1038/s41467-022-28653-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 11
Abstract
Huntington’s disease (HD) results from the abnormal expansion of CAG repeats in exon 1 of the HTT gene. Here, the authors show that orally available, brain penetrant molecule branaplam lowers HTT transcript by promoting inclusion of a poison exon or pseudoexon.
