UCSF scientists have developed a novel biophysical-biochemical screening platform to identify small molecules that prevent the oligomerization of alpha-synuclein: the rate-limiting step in the formation of toxic fibrils in the pathologies of Parkinson’s disease, Lewy Body Dementia, and other neurodegenerative diseases. With this technology, novel families of small molecules have been found with the capacity to reverse multiple pathogenic markers of disease progression in cells.
Parkinson’s disease and other synucleinopathies are characterized by oligomerization and aggregation into larger fibrils of the protein alpha-synuclein. Multiple lines of evidence have pointed to the formation of pre-fibril oligomers as directly contributing to the pathologies of these disorders in addition to forming the building blocks of fibrils themselves. Therapies that could stabilize the monomeric, pre-oligomer state of alpha-synuclein would have the capacity to halt and potentially reverse this pathogenic state.
Using Surface Plasmon Resonance (SPR) technology to measure drug-target binding, and novel biochemical assays for direct measurements of oligomerization (including bioluminescent fragment complementation and FRET), UCSF scientists have identified families of small molecules that directly prevent oligomerization of alpha-synuclein. In cell-based assays of pathogenesis, these small molecules demonstrate the capacity to reverse oligomerization.
To develop & commercialize the technology as:
Under CDA / NDA