Personalized stem cell model offers fast, individualized drug testing for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fast-progressing neurodegenerative disease with an average survival time of three years. In ALS, certain types of neurons called motor neurons that are required for muscle contractions die off, leading to progressive paralysis affecting most muscles of the body. The molecular causes of ALS are poorly understood, and effective treatments are missing.

To study ALS in the lab, Hideyuki Okano and his colleagues from Keio University, Japan, developed a new method to make motor neurons from stem cells taken directly from ALS patients. The results were published today in the journal Stem Cell Reports.

Since timing is key to helping individual patients, Okano’s team optimized their method to obtain functional and mature motor neurons in only two weeks. Intriguingly, just like in patients, the cultured ALS motor neurons had increased susceptibility to cell death compared to neurons from healthy people, underscoring the utility of this system to identify potential drugs to delay or prevent these motor neuron deaths.

To automatize the analysis of these cells, the researchers teamed up with the Japanese company Nikon that developed a specialized software to track neuron survival in cultures over time, thus enabling this assay to be used as a high-throughput screen to identify potential drugs.

Notably, the investigators applied this new method to investigate the drug responses of sporadic ALS patients, as reported in Morimoto’s 2023 article in Cell Stem Cell, and demonstrated a correlation between the iPSC model and patient phenotypes related to drug response.

Researchers hope that this new lab-based model of ALS will help to identify new treatments tailored to each individual patient in a sufficiently short timeframe to slow down disease progression, prolong survival, and improve the quality of life.

Provided by
International Society for Stem Cell Research