Evidence suggests that levodopa’s efficacy and side effects (uncontrolled movements called dyskinesia) are caused by activating dopamine D1 receptors. An optimal Parkinson’s disease therapy would selectively activate the cellular pathways downstream of D1 receptors for efficacy without dyskinesia. Using Sinopia’s machine learning platform, we identified a downstream target and a drug (SB-0107) to modulate that target. In Parkinson’s models, the efficacy of a combination of SB-0107 and non-therapeutic doses of levodopa were equivalent to or superior to higher doses (up to 3x) of levodopa alone, with little to no dyskinesia.
We will assess whether the use of SB-0107 shows promise for both motor and non-motor symptoms of Parkinson’s disease in a large Parkinson’s model.
This study will consist of three parts. First, we will assess the pharmacokinetics of SB-0107 to determine an appropriate dose for the study. Second, we will assess the effects of SB-0107 on motor symptoms, as well as its potential dyskinesia liability. Third, we will assess SB-0107’s effects on non-motor symptoms.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
SB-0107 may change how Parkinson’s disease is treated at all stages of the disease. Early-stage patients could receive a combination of SB-0107 and levodopa that has equivalent or superior efficacy to their current treatment but may avoid dyskinesia complications. Later-stage patients with motor fluctuations may have SB-0107 add-on therapy to reduce “off” time when symptoms are not well controlled. Finally, SB-0107 could potentially be used for patients with non-motor symptoms.
Next Steps for Development:
Successful completion of this study will provide confidence for moving SB-0107 into clinical trials. Pharmacokinetics results will aid with dose selection and understanding drug tolerability. Efficacy results will aid deciding on the types of patients to recruit and the endpoints to pursue.