Description:
Unmet Need
Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized with misfolded α-synuclein (α-syn) accumulation in Lewy bodies (LB). Although some α-syn mutations have been associated with familial PD, the majority cases are sporadic with unknown etiology. Tremendous efforts have been made to develop a sporadic PD model with α-syn spreading model for mechanism study and therapeutic development. The α-syn preformed fibrils (PFF) model is groundbreaking that a single injection of recombinant α-syn PFF can replicate LB-like pathology spreading, neurotoxicity and motor/non-motor dysfunction in wildtype mice. The PFF model can perfectly mimic the sporadic PD; however, limited nanomaterials have been reported to prevent prion-like spread. Another critical issue is the biological effect of nanomaterials. Metal oxides nanoparticles are prone to cause uncertain biological effects due to unstable multivalent metals on the surface. Therefore, there is a critical need to explore the potential of metal alloy nanozymes in preventing prion-like spreading induced by oxidative stress in the sporadic PD model.
Technology Overview
Johns Hopkins researchers have proposed a series of in nitro and in vivo experiments to address the question that nanozyme can prevent prion-like spreading. The report has shown that the PtCu nanoalloys (NAs) functionally mimic three redox enzymes, including peroxidase, catalase and superoxide dismutase and demonstrate superior antioxidant capability in a cell-free system. Furthermore, we tested the effects of PtCu NAs in sporadic Parkinson’s disease (PD) models by using recombinant α-synuclein (α-syn) preformed fibrils (PFF). Treatment with the PtCu NAs significantly reduced the α-syn PFF-induced ROS in mouse primary cortical neurons, and subsequently decreased α-syn PFF-induced pathology and neurotoxicity. Moreover, we’ve found that the treatment with PtCu NAs significantly blocked pathologic α-syn cell-to-cell transmission in microfluidic chambers and in intrastriatal α-syn PFF injection model of PD. These data, taken together, have shown that biocompatible PtCu NAs have therapeutic potential to prevent pathologic α-syn cell-to-cell transmission in PD and related α-synucleinopathies.
Stage of Development
The in nitro and in vivo experiments data has been developed.
Publications
Liu Y-Q, et al., Nanotoday, Volume 36, 101027, 2021
