Researchers at Keio University, Japan, led by Hideyuki Okano, have developed a new method for culturing functional spinal lower motor neurons (LMNs) from induced pluripotent stem cells (iPSCs) sourced from amyotrophic lateral sclerosis (ALS) patients.

The cultured LMNs exhibited ALS-specific pathologies, including abnormal protein aggregations and reduced survival rates compared to healthy cells, effectively mirroring the responses seen in ALS patients.

Okano's team optimized their technique to generate functional and mature motor neurons within just two weeks, emphasizing the urgency of timely treatment for ALS patients.

Using a combination of small molecules and transcription factor transduction, the researchers achieved an impressive 80% induction efficiency of LMNs in this short timeframe, significantly faster than traditional methods.

Their methodology, published in Stem Cell Reports, aims to enhance research and drug screening for ALS, particularly focusing on sporadic cases that account for over 90% of ALS diagnoses.

This new method was employed to assess drug responses in sporadic ALS patients, revealing a correlation between the iPSC model and patient drug response phenotypes, as noted in a previous study by Morimoto.

The ultimate goal of this innovative lab-based model is to facilitate the identification of new treatments tailored to individual ALS patients, potentially slowing disease progression, prolonging survival, and improving quality of life.

The cultured ALS motor neurons displayed increased sensitivity to cell death, reflecting the condition of neurons from healthy individuals and demonstrating the model's potential for drug discovery.

To enhance neuron analysis, the researchers collaborated with Nikon to create specialized software that tracks neuron survival over time, enabling high-throughput screening for potential drugs.

Despite these advances, the research acknowledges limitations, including the need for real-time monitoring systems to ensure reproducibility and manage variability in neuronal differentiation.

Morimoto highlighted the importance of automation and reproducibility in ALS research, which could lead to more accessible and scalable studies.

Future research will focus on modeling ALS cell responses to treatments and exploring the pathomechanism of sporadic ALS, addressing the high heterogeneity among ALS patients.