Rapid Identification and Validation of Novel Rheumatoid Arthritis Drug Treatments using an Integrative Bioinformatics Platform

Daugherty, A. C.; Farrington, C.; Hakin, I.; Mujahid, S.; Noblin, E. S.; Radin, A. M.; Chua, M.-S.; Rabe, M.; Fernald, G.; Ford, D.; Sirota, M.; Schaevitz, L.; Radin, A. A.

doi:10.1101/243998

bioRxiv · 10.1101/243998

Rapid Identification and Validation of Novel Rheumatoid Arthritis Drug Treatments using an Integrative Bioinformatics Platform

Daugherty, A. C.·Farrington, C.·Hakin, I.·Mujahid, S.·Noblin, E. S.·Radin, A. M.·Chua, M.-S.·Rabe, M.·Fernald, G.·Ford, D.·Sirota, M.·Schaevitz, L.·Radin, A. A.

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Abstract

The majority of drugs currently used to treat rheumatoid arthritis (RA) act on a small number of immunomodulatory targets. We applied an integrative biomedical-informatics-based approach and in vivo testing to identify new drug candidates and potential therapeutic targets that could form the basis for future drug development in RA. A computational model of RA was constructed by integrating patient gene expression data, molecular interactions, and clinical drug-disease associations. Drug candidates were scored based on their predicted efficacy across these data types. Ten high-scoring candidates were subsequently screened in a collagen-induced arthritis model of RA. Treatment with exenatide, olopatadine, and TXR-112 significantly improved multiple preclinical endpoints, including animal mobility which was measured using a novel digital platform. These three drug candidates do not act on common RA therapeutic targets; however, links between known candidate pharmacology and pathological processes involved in RA suggest hypothetical mechanisms contributing to the observed efficacy.

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Daugherty, A. C., Farrington, C., Hakin, I., Mujahid, S., Noblin, E. S., Radin, A. M., Chua, M.-S., Rabe, M., Fernald, G., Ford, D., Sirota, M., Schaevitz, L., Radin, A. A.. 2018-01-07. Rapid Identification and Validation of Novel Rheumatoid Arthritis Drug Treatments using an Integrative Bioinformatics Platform. https://doi.org/10.1101/243998

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