Recycled Translation: Repurposing Drugs for Stroke.
Samantha E SpellicyDavid C HessPublished in: Translational stroke research (2022)
Stroke, which continues to be a leading cause of death and long-term disability worldwide, has often been described as a clinical graveyard. While multiple small molecule therapeutics have undergone clinical trials in stroke, currently only one Food and Drug Administration (FDA)-approved medication exists for the treatment of stroke, the biological, recombinant tissue plasminogen activator (rt-PA). Repurposing of therapeutics which have previously gained FDA approval for alternative indications serves as a prospective option for stroke therapeutic translation. In contrast to de novo drug development, repurposing strategies have patient-centered and economic advantages. These include increased safety, increased chance of approval, decreased time to approval, and decreased capital investment. Presently, 37 active stroke clinical trials utilize repurposed therapeutics with various initial indications and dosing paradigms. The currently studied repurposed therapeutics fall into six mechanistic categories: (1) anticoagulation; (2) vasculature integrity, response, or red blood cell (RBC) alterations; (3) immune system regulation; (4) neurotransmission; and (5) neuroprotection. Directed hypothesis-driven computational investigation utilizing drug databases, in silico drug-protein interaction modeling, genomic data, and consensus methodology can determine if the current mechanistic repurposing categories have the highest chance of translational success or if other mechanistic avenues should be explored. With this increased focus on repurposed therapeutic strategies over de novo strategies, evolution and optimization of regulatory protections are needed to incentivize innovators and investigators.
Keyphrases
- atrial fibrillation
- small molecule
- drug administration
- clinical trial
- red blood cell
- cerebral ischemia
- healthcare
- multiple sclerosis
- protein protein
- magnetic resonance
- clinical practice
- emergency department
- venous thromboembolism
- brain injury
- risk assessment
- subarachnoid hemorrhage
- combination therapy
- phase ii
- machine learning
- human health