Parkinson’s Disease is a brain disorder that becomes worse with time. Multiple therapies treat its symptoms like tremors, stiffness, and lack of coordination. A pre-synaptic neural protein called α‐synuclein(αS) is targeted. It is a genetic cause that accumulates in vesicles and lipid membranes. This study assesses inhibitors that prevent αS proliferation into cultured human neurons.
The objective of the study is to assess the stearoyl‐CoA desaturase (SCD) inhibitor (“5b”). Non-tg mice with WT human αS were the subjects. They received an oral dose of 5b in drinking water. Mice with amplified and familial PD αS mutation was also a part of the trial. Nigral and cortical neurodegeneration onset and robust PD-like motor syndrome in 3K were evaluated. A 5b vs. placebo mice comparison quantified motor phenotypes, brain cytopathology, and SCD-related lipids changes. The outcomes were compared to the effects of crossing 3K to SCD1 mice.
The 5b therapy lowered αS hyperphosphorylation in E46K‐expressing neurons in humans. It also lowered in 3K neural cultures of the WT and 3K αS mice. 5b also blocked mild gait deficits. It reduced PD‐like resting tremor and the motor decline in 3K αS mice. It also increased αS tetramers and decreased the PK‐resistant lipid‐rich aggregates. The same benefits validated targets after genetic deletion of 1 SCD allele.
Prolonging low SCD activity in the brain prevents PD symptoms in multiple models. The oral SCD inhibitor has the potential to treat αS in humans.