SIMPATHIC: Accelerating drug repurposing for rare diseases by exploiting SIMilarities in clinical and molecular PATHology

Abstract

Rare diseases affect over 400 million people worldwide, with approved treatment available for less than 6 % of these diseases. Drug repurposing is a key strategy in the development of therapies for rare disease patients with large unmet medical needs. The process of repurposing drugs compared to novel drug development is a time-saving and cost-efficient method potentially resulting in higher success rates. To accelerate and ensure sustainability in therapy development for rare neurometabolic, neurological, and neuromuscular diseases, an international consortium SIMilarities in clinical and molecular PATHology (SIMPATHIC) has been established where we move away from the one drug one disease concept and move towards one drug targeting a pathomechanism shared between diseases, by applying parallel preclinical and clinical drug development. Here the consortium describes accelerators of drug repurposing pursued by the consortium, including 1) co-creation, 2) patient empowerment, 3) use of standardized induced pluripotent stem cell (iPSC)-derived disease models and cellular and molecular profiling, 4) high-throughput drug screening in neurons, 5) innovative clinical trial design, and 6) selection of appropriate exploitation and patient access models. In this way, a fast and effective drug repurposing pathway for several rare diseases will be established to reduce time from discovery to patient access.

Keywords: Basket trial; Drug repurposing; Drug screening; Induced pluripotent stem cells; Rare diseases; Therapy development.