Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin-Angiotensin System
Abstract
The results we have thus far generated support our hypothesis that skewing of the regulatory arm of RAS in the CNS following onset of demyelinating injury in mice is beneficial. We observed in an animal model of multiple sclerosis that the RAS system is pertubated to bias the regulatory arm in the progressive phases of the disease. We demonstrated not just an increase in expression of specific receptors, but also angiotensin metabolites. The regulatory arm of RAS was activated in an effort to stimulate repair once the immunological and pathological destruction of the tissue had reached a tipping point. We also demonstrated for the first time that there is differential regulation of the RAS pathway in different regions of the CNS; likely driven by the extent of the pathological insult. Our data show that a natural response to the damage that occurs in EAE is to skew expression of the RAS system in the brain to the anti-inflammatory, regulatory arm. In our proposal we hypothesized that if we were to administer A1-7 at an earlier stage in the disease we could activate the regulatory arm of RAS at an earlier stage and prevent significant tissue damage. We have shown that administration of an optimal dose of A1-7 at the first sign of clinical disease significantly ameliorated disease course in mice. These data support our hypothesis and would support the development of A1-7 as a potential treatment for multiple sclerosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1002669
Entities
People
- Brett T Lund
Organizations
- University of Southern California