Antisense oligonucleotides targeting valosin‐containing protein ameliorate muscle pathology and molecular defects in cell and mouse models of multisystem proteinopathy
VCP multisystem proteinopathy 1 is caused by gain-of-function pathogenic variants of the VCP gene. VCP targeting ASOs were well tolerated and significantly reduced VCP, TAR DNA binding protein 43 (TDP 43), and autophagy protein expression in the (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). The ASOs reduced VCP, TDP-43, and autophagy flux expression, and improved functional tests of muscle strength in the humanized VCP A232E mice.
Authors
- Michele Carrer (ORCID: https://orcid.org/0000-0002-6464-9584)
- Megan Afetian (ORCID: https://orcid.org/0009-0005-4318-1598)
- Mariam Youssef (ORCID: https://orcid.org/0000-0002-8516-7058)
- Olga G. Jaime
- Pallabi Pal
- Yasamin Fazeli (ORCID: https://orcid.org/0000-0001-6477-3369)
- Virginia Kimonis (ORCID: https://orcid.org/0000-0003-1567-4449)
- Tamar R. Grossman
- Lan Weiss (ORCID: https://orcid.org/0000-0003-4130-8725)
- D. Andries Bosch (ORCID: https://orcid.org/0009-0008-5354-8279)
- Alyaa Shmara (ORCID: https://orcid.org/0000-0001-8667-6754)
- Paymaan Jafar‐Nejad (ORCID: https://orcid.org/0000-0001-5176-739X)
- Victoria Boock
- Cheng Cheng (ORCID: https://orcid.org/0000-0002-5007-4695)
- Michael R. Hicks (ORCID: https://orcid.org/0000-0002-1069-5075)
Institutions
- University of California, Irvine (US)
- Ionis Pharmaceuticals (United States) (US)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/ctm2.70530
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Muscular Dystrophy Association