Type I PRMT Inhibitor Preclinical Pharmacology for ALS
Abstract
This proposal aims to identify one or two drugs, MS023 and GSK715, for clinical development for people with ALS. The proposal builds on research by the applicants and others supporting the idea that inhibiting a family of enzymes called Type I PRMTs could be helpful for people with ALS, specifically, but NOT limited to C9orf72 ALS. PRMTs are enzymes that change a specific amino acid, arginine, that is a part of many proteins in humans and all living things on earth. The changes to the arginine, called methylation, can change the functions of the proteins in important ways. The changes seem implicated in many of the processes that seem to go wrong in ALS. If the proposal is successful, it will identify drugs that could slow or stop ALS disease progression. In addition, the proposal will innovate using a mouse model of C9orf72-associated that has not yet been applied to drug testing. If this proposal succeeds, that mouse model could be used to identify future treatments for C9orf72 ALS. Finally, this proposal will result in the confirmation of asymmetric dimethylarginine in blood as a biomarker indicating that the drugs are hitting their desired target. The projected time that it might take to achieve a patient related outcome is realistically between 3 and 7 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210192
Entities
People
- Fernando Vieira
Organizations
- ALS Therapy Development Institute
- United States Army