Study Rationale: Previous research has found that a type of fat molecules, called unsaturated fatty acids, are important regulators of toxicity in brain cells caused by the protein alpha-synuclein – a key part of Lewy bodies, which are clumps of proteins, fats and cellular organelles typically found in Parkinson’s disease (PD) patients. Reducing a key enzyme in the brain, Stearol-CoA-Desaturase (SCD), responsible for the production of these unsaturated fatty acids, can become a potential drug to treat PD, as this protects human brain cells from harmful effects caused by alpha-synuclein.
Hypothesis: We hypothesize that inhibiting the cellular production of the enzyme Stearoyl-CoA-Desaturase will reduce the build-up of unsaturated fatty acids and prevent harmful effects caused by alpha-synuclein in the human brain.
Study Design: RNA interference (RNAi) is a breakthrough in understanding how genes are controlled and is a natural pathway in all cells involved in regulating how a gene is made into proteins. This new class of medicines, called RNAi therapeutics (RNAiTh), has the potential to block the production of disease-causing proteins by targeting the messenger RNA transcript of any gene. We are designing RNAiTh to target an enzyme, SCD, in order to protect human brain cells from the harmful effects caused by alpha-synuclein in PD. The RNAiTh candidates will be tested in PD models to ensure that we are on the right path to make a potential drug.
Impact on Diagnosis/Treatment of Parkinson’s disease: RNAiTh against SCD is chosen based on many scientific contributions over the past few years, which suggest that targeting SCD may be protective in PD progression.
Next Steps for Development: Convincing in vivo data from our study would justify progression into clinical trials, using molecules similar to the ones tested in this study.