UB-312, an investigational active immunotherapy targeting α-synuclein, enhances survival of a peripherally-seeded mouse model of synucleinopathy

Abstract Synucleinopathies are neurodegenerative diseases that exhibit pathological inclusions predominantly composed of misfolded α-synuclein (αsyn) protein. Parkinson’s disease, Lewy body dementia, and multiple system atrophy are the most common synucleinopathies and affect millions of people in the United States, yet there is a paucity of disease-modifying treatments. αsyn-targeting active immunotherapy UB-312 was created to meet this unmet need, aimed at clearing pathological αsyn and ultimately slowing disease progression. Phase I clinical trial results demonstrated good tolerability and immunogenicity of UB-312 in a Parkinson’s patient population. To further evaluate the efficacy of UB-312, we performed in vivo experimentation in the peripherally seeded M83 +/− mouse model of synucleinopathy. Results demonstrate that intramuscular administration of UB-312 elicits an anti-αsyn immune response and increases survivability in M83 +/− mice. These positive findings merit further studies investigating UB-312 as a candidate active immunotherapy for synucleinopathies.