Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients

Abstract

This study aimed to assess the naturally occurring variation in plasma fatty acids in healthy subjects and Parkinson’s disease (PD) patients. Alpha-synuclein (aSyn) plays a major role in Parkinson’s disease. Inhibition of stearoyl-CoA desaturase (SCD) reduces levels of mono-unsaturated C16 and C18 fatty acids, which are involved in aSyn toxicity in vitro and in vivo. The ratio of mono-unsaturated to saturated fatty acids (fatty acid desaturase index (FA-DI)) in plasma after SCD-inhibition correlates with effects on brain FA-DI. However, the FA-DI normal values and the inter- and intra-day variation in PD-patients and healthy subjects is unknown. Ten PD-patients (54 –73 years) and ten age-matched healthy subjects were included. On three consecutive days, fatty acids fractions and concentrations were measured throughout the day. Outcomes are expressed as estimated mean, and the coefficient of variation (CV%) in percentage. For C16 FA-DI, the inter-subject CV% was 20.7 % in healthy subjects, and 37.7 % in PD-patients. The intra-subject CV% over days was 14.0 % in healthy subjects, and 14.2 % in PD-patients, and within days 5.1 % in healthy subjects, and 5.9 % in PD-patients. For C18 FA-DI, the inter-subject CV% was 14.8 % in healthy subjects, and 16.0 % in PD-patients. The intra-subject CV% over days was 11.0 % in healthy subjects, and 8.6 % in PD-patients, and within days 8.4 % in healthy subjects, and 6.7 % in PD-patients. The observed extent of variability in healthy subjects and PD-patients support C16 and C18 FA-DI as suitable biomarkers to demonstrate target engagement in plasma, of for example SCD-inhibitors, in both healthy subjects and PD-patients.