Repurposing of Drugs in Autoimmune Diseases: From Serendipity to System Reset

Drug repurposing, also known as drug retasking is the process of identifying new therapeutic indications for existing medications. It has been a vital strategy in rheumatology with continuing contributions even today. This approach is particularly useful in rheumatic diseases because de Novo drug development is plagued by exorbitant costs, high attrition rate and prolonged timelines. Historically, the successful repositioning of completely off-target drugs such as antimalarials, steroids followed by transformative repositioning of methotrexate from a chemotherapeutic drug to as a gold standard disease-modifying antirheumatic drug (DMARD) which laid the foundation for drug repurposing in rheumatology. However, the scenario has changed today with heavy reliance on advanced computational frameworks. Modern strategies leverage drug-centric molecular docking, and using molecular techniques like transcriptomics to systematically predict drug-disease associations based on shared biological pathways. Despite these technological advancements, a number of hindrances exist like intellectual property barriers, lack of commercial incentives for off-patent compounds, and fragile academia-industry collaborations. Ultimately, it is required to integrate policy reforms with novel research frameworks for facilitating the trials of repurposed compounds for patients with high unmet medical needs. This review explores the historical perspectives and current landscape of drug repurposing in rheumatic diseases highlighting the transition from serendipitous clinical discoveries to systematic, data-driven methodologies and stresses upon the ongoing need of drug repositioning to bypass the bottlenecks in traditional drug development.

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