https://www.selleckchem.com/products/AS703026.html Genetic defects of the type I interferon pathway are also linked to a more clinically severe phenotype of COVID-19. Finally, dysregulation of the adaptive immune system may also play a role in the severity and complex clinical course of patients with COVID-19. A better understanding of the host immune responses to SARS-CoV-2 will hopefully lead to new treatment modalities to prevent the poor outcomes of COVID-19 in those individuals with pre-existing risk factors or genetic variants that contribute to the dysregulated host immune responses. The randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP). All patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO. Eighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n=4) and fatigue (n=2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n=55) showed a mean (SD) change from DBP baseline in daily OFF time of -3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (±SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543mg