Evaluation of PPAR-Delta/Gamma Agonist Therapy as a Novel Treatment Paradigm for ALS
Abstract
In this Therapeutic Idea Award proposal application, we will conduct proof-of-concept studies to evaluate the therapeutic potential of a dual PPAR-delta/gamma nuclear receptor agonist, T3D-959, to ameliorate ALS neurotoxicity. This will be accomplished by pursuit of the following two Specific Aims. In Aim #1, we will test the hypothesis that T3D-959 can prevent ALS disease-relevant phenotypes in primary cortical neuron models. We will employ two different ALS neurotoxicity systems, which recapitulate key features of ALS disease pathology in sporadic ALS and in the most common form of familial ALS. In Aim #2, we will test the hypothesis that T3D-959 can rescue ALS disease phenotypes in two different mouse models, the PrP-TDP-43:Q331K transgenic mouse and the (G4C2)-149 repeat C9orf72 mouse model. We will perform two preclinical trials, after establishing a safe, effective dose and route of delivery for T3D-959. Preclinical trial read-outs will be to evaluate general health of T3D959-treated ALS mice in comparison to vehicle-treated ALS mice; neuromuscular and cognitive function; histopathology; and disease-specific molecular pathology read-outs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2023
- Accession Number
- AD1208694
Entities
People
- Albert R. La Spada
Organizations
- University of California, Irvine