Maiden voyage: induced pluripotent stem cell-based drug screening for amyotrophic lateral sclerosis

Using patient-derived induced pluripotent stem cells, neurodegenerative disease phenotypes have been recapitulated and their pathogenesis analysed leading to significant progress in drug screening. In amyotrophic lateral sclerosis, high-throughput screening using induced pluripotent stem cells-derived motor neurons has identified candidate drugs. Owing to induced pluripotent stem cell-based drug evaluation/screening, three compounds, retigabine, ropinirole, and bosutinib, have progressed to clinical trials. Retigabine blocks hyperexcitability and improves survival in amyotrophic lateral sclerosis patient-derived motor neurons. In a randomized clinical trial (n = 65), treatment with retigabine reduced neuronal excitability after 8 weeks. Ropinirole, identified in a high-throughput screening, attenuates pathological phenotypes in patient-derived motor neurons. In a trial limited by a small sample size (n = 20), ropinirole was tolerable and had clinical benefits on function and survival. A phase 1 study of bosutinib has reported safety and tolerability for 12 weeks. Thus, these clinical trials show safety and positive effects and confirm the reliability of stem cell-based drug discovery. This novel strategy leads to reduced costs and time when compared to animal testing and opens new avenues for therapy in intractable diseases. Ito et al. provide an overview of the current status and future potential of drug screening and development for amyotrophic lateral sclerosis based on patient-derived induced pluripotent stem cells, including recent clinical trials of retigabine, ropinirole, and bosutinib.

Automated summary

Significant progress has been made in drug screening for amyotrophic lateral sclerosis using patient-derived induced pluripotent stem cells, leading to the identification of candidate drugs and the advancement of clinical trials. This stem cell-based approach shows safety and positive effects, reducing costs and time compared to animal testing.