Drug Side Effects
Sinopia Biosciences has developed a proprietary, state-of-the art systems biology and bioinformatics platform to study the efficacy and safety of therapeutics at an unprecedented level of biochemical detail.
We are currently pursuing two areas in healthcare
Levodopa is the most effective treatment for Parkinson’s disease but has long-term liabilities including its main side effect levodopa induced dyskinesia. Using Sinopia’s platform, we determined the pathways that are implicated in levodopa’s beneficial effects and dyskinesia. We have identified a drug repurposing small molecule with a unique mechanism of action that selectively potentiates levodopa’s beneficial effects without causing dyskinesia. In multiple preclinical efficacy experiments, this compound shows consistent and unparelleled potency. Further, the compound in combination with low dose levodopa can fully treat rodent symptoms in chronic administration without inducing dyskinesias.
Red blood cells and platelets are integral blood products for modern medicine with nearly 100 million units transfused per year. These cells undergo biochemical, physicochemical, and morphological changes during storage that may affect the quality and safety of transfusion. Sinopia’s platform has aided in better understanding the breakdown of these cells and we are pursuing novel media solutions to ameliorate these issues to improve safety and efficacy of transfusions.
Paglia G, D'Alessandro A, Rolfsson O, Sigurjonsson OE, Bordbar A, Palsson S, Nemkov T, Hansen KC, Gudmundsson S, Palsson BO. "Biomarkers defining the metabolic age of red blood cells during storage" Blood Early View (2016).
Bordbar A, Johansson PI, Paglia G, Harrison SJ, Wichuk K, Magnusdottir M, Valgeirsdottir S, Gybel-Brask M, Ostrowski SR, Palsson S, Rolfsson O, Sigurjonsson OE, Hansen MB, Gudmundsson S, Palsson BO, "Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes" Transfusion, 56(4):852 (2016).
Bordbar A, McCloskey DM, Zielinski DC, Sonnenschein N, Jamshidi N, Palsson BO, "Personalized whole-cell kinetic models of metabolism for discovery in genomics and pharmacodynamics" Cell Systems, 1:283 (2015).
Zielinski DC, Filipp F, Bordbar A, Smith J, Herrgard M, Mo ML, Palsson BO, "Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side-effect pathogenesis" Nature Communications, 6:7101 (2015).
Paglia G, Sigurjonsson OE, Rolfsson O, Valgeirsdottir S, Hansen MB, Brynjolfsson S, Gudmundsson S, Palsson BO, "Metabolomic analysis of platelets during storage: a comparison between apheresis- and buffy coat-derived platelet concentrates" Transfusion, 55(2):301 (2015).
Paglia G, Sigurjonsson OE, Rolfsson O, Valgeirsdottir S, Hansen MB, Brynjolfsson S, Gudmundsson S, Palsson BO, “Comprehensive metabolomics study of platelets reveals the expression of discrete metabolic phenotypes during storage” Transfusion, 54(11): 2911 (2014).
Bordbar A, Monk JM, King ZA, Palsson BO, "Constraint-based models predict metabolic and associated cellular functions" Nature Reviews Genetics, 15(2):107 (2014).
Thomas A, Rahmanian S, Bordbar A, Palsson BO, Jamshidi N, “Network reconstruction of platelet metabolism identified metabolic signature for aspirin resistance” Scientific Reports, 4:3925 (2014).
Paglia G, Palsson BO, Sigurjonsson OE. “Systems biology of blood cells: Can it help to extend the expiration date?” Journal of Proteomics, 76:163-167 (2012).
Bordbar A, Jamshidi N, Palsson BO. "iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states" BMC Systems Biology, 5:110 (2011).
Joshi A and Palsson BO. "Metabolic dynamics in the human red cell: Part I-A comprehensive kinetic model” Journal of Theoretical Biology, 152(2):285-286 (1989). (Parts II, III, IV)