DR15 Inhibitor for MS
DR15 Inhibitor for Goodpasture's/Anti-GBM
Goodpasture’s disease/anti-glomerular basement membrane disease (anti-GBM) is a rare, orphan autoimmune disease affecting the kidney and lung. Incidence is 1-2/million population.
Disease is strongly associated with DR15
Results:
The DR 15 antagonist PV-267 inhibits autoreactivity to the immunodominant T cell epitope antigen, α3135-145, and attenuates disease in experimental autoimmune anti-GBM disease in DR15 transgenic mice. Studies by Ooi, J et al., Monash University.
DR15 Inhibitor for Parkinson's
In prodromal stages of Parkinson’s disease, the alpha-synuclein peptide antigen, a-syn 32-46 binds to the disease-associated MHC class II HLA-DRB1*15:01 triggering autoimmune pathology (gut, ENS).
See: Garretti F, Monahan C, Sloan N, Bergen J, Shahriar S, Kim SW, Sette A, Cutforth T, Kanter E, Agalliu D, Sulzer D. Interaction of an α-synuclein epitope with HLA-DRB1∗15:01 triggers enteric features in mice reminiscent of prodromal Parkinson’s disease. Neuron. 2023 Nov 1;111(21):3397-3413.e5. doi: 10.1016/j.neuron.2023.07.015. Epub 2023 Aug 18. PMID: 37597517; PMCID: PMC11068096.
PV-3212 is a potent small molecule blocker of antigen binding and presentation to DRB1*15:01 and currently in preclinical development for multiple sclerosis. Its unique antagonist mechanism action will be evaluated in the a-synuclein models in vitro and in transgenic mice to assess its efficacy in cellular and mouse models to determine its potential in treatment of prodromal PD.
