Optimization of a small molecule to inhibit a-synuclein aggregation in MSA

No disease-modifying treatment is available for multiple system atrophy (MSA). The cytopathological
hallmark of MSA is the accumulation of a-synuclein (aSyn) protein aggregates forming glial cytoplasmic
inclusions. The aggregated form of aSyn plays a central role in the pathogenesis of MSA. Thus, there is the
hope that drugs that prevent or revert aSyn aggregation might alter MSA progression by preventing,
blocking, or slowing neurodegeneration. We identified SynuClean-D (SC-D), a small molecule that
interrupts aSyn aggregation, disentangles mature fibrils, and hampers the propagation of aggregated aSyn.
The agglutination of all these synergic properties in a single scaffold endorses SC-D with significant
neuroprotective activity. This project aims to evolve this candidate into a drug able to penetrate the brain
efficiently and potentially prevent the progression of neurological damage. In a subsequent stage of the
project, the molecule's activity will be validated in a preclinical model of MSA that reproduces the specific
pathology of this disorder in the mouse brain. If successful, this preclinical proof of concept could form a
basis for clinical trials in people living with MSA.