Targeting CNS Expression of Chitinases as a Novel Therapy for ALS
Abstract
A well-known feature of amyotrophic lateral sclerosis (ALS) is the presence and activation of inflammation and inflammatory signaling pathways within the brain and spinal cord. While increased inflammation is present in ALS patients, drugs that target inflammation have not proven effective in clinical trials. One reason is that most anti-inflammatory drugs target general features of inflammation and not key factors of inflammation that drive neuronal death. One key factor of inflammation are a family of proteins called chitinases that are expressed by cells of the immune system. We and others discovered that chitinases are expressed and released by specific glial cell types during inflammation and present in high levels in cerebrospinal fluid of ALS patients. In this project we will develop novel viral based vectors (adeno-associated virus or AAV) that target specific cell populations to either turn on or turn off chitinase gene expression. Through this method we will regulate the bad chitinase signals while preserving and expanding the good chitinase signals, and will test this therapeutic approach in the mutant SOD1G93A mouse model. We will also further develop biomarker tests that measure each chitinase protein in human blood and cerebrospinal fluid. These chitinase biomarker tests will enable us to target our approach to ALS patients with high levels of chitinases and to monitor the therapeutic impact of our viral vector based treatments in biofluids collected after treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1210800
Entities
People
- Robert Bowser
Organizations
- Dignity Health