The Effects of SKF-835666 on Levodopa-Induced Dyskinesia in Drosophila melanogaster

Abstract

Although levodopa is considered the "gold standard" medication for Parkinson's disease, it is flawed as almost 90% of patients contract a side effect known as Levodopa Induced Dyskinesia (LID) after 10 years of treatment. LID manifests as involuntary movements and muscle spasms and presently lacks a cure. Previous studies on Drosophila melanogaster models have found that epigenetically inhibiting the ADCY2 gene reduces LID symptoms as represented by abnormal involuntary movements. Consequently, this study sought to assess the therapeutic potential of SKF-83566, an ADCY2 inhibitor, in ameliorating LID symptoms within a D. melanogaster model. The primary objective was to quantify the drug's impact by implementing Abnormal Involuntary Movements (AIMs) assay. This study found that wild-type flies on a diet of 10 mM of levodopa had a statistically significant increase in AIMs scores when compared to normal flies, implying that they successfully modeled LID. Furthermore, the data from this study supports that SKF-83566 alleviates LID symptoms, as flies with LID had lower AIMs scores when given SKF-83566. Moreover, findings from this study indicate that the locomotion of healthy D. melanogaster remained unaffected when exposed to a 5 mM dosage of SKF-83566 over a 7-day period. This study presents a novel administration procedure of SKF-83566 which could be applied in future research with D. melanogaster. The demonstrated effectiveness of the compound in reducing LID symptoms within a D. melanogaster model highlights its potential as a treatment option for LID, which could be researched further in the future.