SYN4569

SYN4569 is an orally available, first-in-class small molecule inhibitor of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) being developed by SynuCa Therapeutics, a spinout from Aarhus University. Pathological alpha-synuclein aggregates, which are hallmarks of neurodegenerative disorders such as Parkinson's disease, multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), directly bind to and overactivate SERCA, leading to intracellular calcium dysregulation and impaired autophagy. SYN4569 selectively normalizes this disease-specific gain-of-function state of SERCA, restoring calcium homeostasis and autophagy to enable the clearance of toxic alpha-synuclein aggregates. In preclinical models of multiple system atrophy-cerebellar type (MSA-C), SYN4569 has demonstrated the ability to improve motor behavior, reduce phosphorylated alpha-synuclein aggregates, and prevent demyelination.