Our Research

The key aspect of selective motor neuron death in motor neuron diseases had been difficult to address using available mouse models. We use as main model system a human induced pluripotent stem cell (iPSC)-based approach and discovered that even within a single genetic background, MNs display a wide diversity of SMN levels – protein essential for MN survival –, and that those cells with low SMN are more susceptible to die. This correlation holds true in MNs expressing mutations causing the most common motor neuron diseases (amyotrophic lateral sclerosis or ALS and spinal muscular atrophy or SMA) and even in MNs obtained from unaffected patients.

This discovery led to a new understanding of the importance of cell diversity in the progression of these diseases and helped to explain why there is a “survivor” population of MNs. However, there is so much that we still ignore. Some of the question that we want to answer are: what are the main similarities and differences between the surviving ALS and SMA MNs are there factors/pathways shared between neuronal types unaffected in MNDs that explain their protection?, what is the molecular basis of SMN heterogeneity across MN populations? Ultimately, why do many neurons degenerate while some remain fully resistant?