Therapeutic developments for valosin-containing protein mediated multisystem proteinopathy.

Abstract

PURPOSE OF REVIEW:

Missense mutations in valosin-containing protein (VCP) can lead to a multisystem proteinopathy 1 (MSP1) with any combination of limb-girdle distribution inclusion body myopathy (IBM) (present in about 90% of cases), Paget's disease of bone, and frontotemporal dementia (IBMPFD). VCP mutations lead to gain of function activity with widespread disarray in cellular function, with enhanced ATPase activity, increased binding with its cofactors, and reduced mitofusin levels.

RECENT FINDINGS:

This review highlights novel therapeutic approaches in VCP-MSP in in-vitro and in-vivo models. Furthermore, we also discuss therapies targeting mitochondrial dysfunction, autophagy, TDP-43 pathways, and gene therapies in other diseases with similar pathway involvement which can also be applicable in VCP-MSP.

SUMMARY:

Being a rare disease, it is challenging to perform large-scale randomized control trials (RCTs) in VCP-MSP. However, it is important to recognize potential therapeutic targets, and assess their safety and efficacy in preclinical models, to initiate RCTs for potential therapies in this debilitating disease.

• Authors: Victoria Boock, Bhaskar Roy, Gerald Pfeffer, Virginia Kimonis
• Journal: Current opinion in neurology (Curr Opin Neurol) Vol. 36 Issue 5 Pg. 432-440 (10 01 2023) ISSN: 1473-6551 [Electronic] England
• PMID: 37678339 (Publication Type: Review, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Valosin Containing Protein

Topics

• Humans
• Valosin Containing Protein (genetics)
• Frontotemporal Dementia (genetics, therapy)
• Genetic Therapy
• Muscular Dystrophies, Limb-Girdle (genetics, therapy)