Developing Therapeutic Agents for Nucleotide Repeat Expansion-Mediated ALS
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Unfortunately, the mechanisms underlying this motor neuron degenerative disease remain poorly understood. The research proposed here, if successful, will lead to new therapeutic agents that can help to treat the most common cases of ALS. Discoveries of mutations in genes linked to ALS are accelerating our understanding of the molecular underpinning of this devastating disease. Recently, a genetic anomaly in a gene known as C9orf72 was identified as the most common genetic abnormality associated with both familial and sporadic ALS. The genetic change involves expansion of a short stretch of repeating units that is a normal part of the DNA. While working to understand how this genetic mutation leads to the devastating disease of ALS, we have uncovered a molecular mechanism through which the three-dimensional structures of the DNA can initiate multiple events and wreak havoc in patients cells. Based on our findings, we propose a new strategy to develop therapeutic agents that can provide intervention at the root of the disease and be translated to clinical use quickly. Furthermore, our discovery platform can be applied to other forms of neurodegenerative diseases and ultimately help us to better treat or prevent these devastating diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510069
Entities
People
- Jiou Wang
Organizations
- Johns Hopkins University
- United States Army