Novel naturally occurring autoantibodies attenuate -synuclein pathology in a mouse model of Parkinson's disease

Aims: Accumulation and propagation of pathological alpha-synuclein (alpha-Syn) are the major contributing factors to the pathogenesis of Parkinson's disease (PD). Therapy to halt the spreading of alpha-Syn pathology needs to be established. Methods: After phage display and affinity maturation, human-derived anti-alpha-Syn autoantibodies were selected and applied to biochemical, cellular and animal models of PD. Results: The novel naturally occurring anti-alpha-Syn autoantibodies (alpha-Syn-nAbs), P21 and P22, selectively bind alpha-Syn preformed fibrils (PFFs), recognise Lewy bodies (LBs) and Lewy neurites (LNs) in human PD brains, block a-Syn fibrillization and inhibit the seeding of alpha-Syn PFFs. Moreover, systematic administration of P21 and P22 attenuates alpha-Syn pathology, degeneration of the nigrostriatal pathway and motor deficits in mice injected with alpha-Syn PFFs. Conclusions: P21 and P22 attenuate alpha-synuclein pathology and are promising candidates for PD treatment.