Personalized Insights into ALS Treatment Through Patient-Derived Cell Testing

Researchers from IMDEA Nanociencia in Madrid, along with colleagues from the Margarita Salas Biological Research Center and the University of Oxford, have developed a groundbreaking approach to studying amyotrophic lateral sclerosis (ALS) by using cells directly obtained from patients. Unlike other diseases, ALS has proven difficult to replicate accurately in animal models, which hampers the development of effective therapies. To address this challenge, the team focused on examining human cells, specifically lymphocytes and motor neurons derived from stem cells, from individuals with ALS.

This innovative study aimed to understand how ALS impacts cells at the molecular level, particularly focusing on abnormal protein aggregates outside the cell nucleus—a common hallmark of the disease. The researchers analyzed blood-derived immune cells from 18 patients with both sporadic and genetic forms of ALS, alongside healthy controls. They tested various drugs to see if they could reduce or prevent abnormal protein accumulation, particularly targeting the phosphorylation of TDP-43, a critical protein involved in nerve cell function that often forms pathological aggregates in ALS.

Using ultraviolet light absorbance techniques, the team measured protein aggregation after drug treatments. Results showed that certain compounds could decrease protein buildup in some patients’ cells, while having no effect or even worsening aggregation in others. This variability indicates that patients respond differently to treatments, highlighting the importance of personalized medicine in ALS therapy. Such findings suggest that pre-treatment cell testing could identify the most effective drugs for each patient, reducing unnecessary side effects and increasing therapeutic success.

In collaboration with Professor Talbot from Oxford, the team also generated motor neurons from stem cells of ALS patients. This approach allows for direct laboratory testing of treatments on patient-specific neurons, offering a promising way to discover more targeted and effective therapies. Dr. Valle Palomo emphasized that assessing a patient’s cells directly could significantly enhance treatment precision, as lymphocytes reflect important aspects of the disease’s pathology despite ALS primarily affecting motor neurons.

Currently, over 500 clinical trials are underway for ALS, but experts agree that future progress hinges on detailed molecular characterization of each patient's disease profile. The innovative use of patient-derived cells marks a significant step toward personalized treatment strategies, aiming to improve outcomes and reduce trial-and-error in therapy development.

This research underscores the potential of cell-based models in understanding neurodegenerative diseases and highlights a less invasive method to evaluate and personalize ALS treatment strategies, moving closer to precision medicine in neurology.