Federal Project Grant Award Summary

The National Institute on Aging awarded $431,750 to the University of California, Irvine under the Aging Research program (CFDA 93.866) to conduct research on correcting Valosin-Containing Protein (VCP) multisystem proteinopathy through antisense oligonucleotide (ASO) technology. The project, which commenced May 15, 2026 and is scheduled for completion by April 30, 2028, focuses on developing a therapeutic treatment for the neuromuscular component of VCP disease, an autosomal dominant disorder characterized by inclusion body myopathy, Paget's disease of the bone, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS). Currently, no treatment exists for the neuromuscular manifestations of VCP disease, which causes severe muscle weakness and early mortality.

The research deliverables include preclinical studies utilizing ASO technology designed by Ionis Pharmaceuticals to selectively reduce VCP activity in disease models, with preliminary results demonstrating approximately 48% reduction in VCP messenger RNA expression and 40% reduction in protein expression using the lead ASO candidate (ASO2). This candidate showed improved safety profiles and restoration of normal TDP-43 (TAR DNA-binding protein 43) levels in both patient-derived induced pluripotent stem cell-derived myoblasts and humanized mouse models, establishing the scientific foundation for potential therapeutic intervention in a currently untreated neuromuscular disease.