Amyotrophic lateral sclerosis (ALS) is a diverse neurodegenerative disorder affecting motor neurons and voluntary muscle control. Despite the identified mutations in specific genes defining different ALS subtypes, the potential impact of specific immune features on ALS heterogeneity remains poorly understood.

In this episode, we delve into the compelling work of Dr. Campisi, who explores ALS-4, an ALS subtype characterized by juvenile onset and slow progression. ALS4 is caused by mutations in the senataxin gene (SETX), and Dr. Campisi's study utilizing Setx knock-in mice reveals intriguing links between this ALS subtype and the immune system.

Dr. Campisi has identified an immunological signature in ALS4, consisting of clonally expanded, terminally differentiated effector memory (TEMRA) CD8 T cells in the central nervous system and the blood of these mice. Intriguingly, these increased frequencies of antigen-specific CD8 T cells parallel the progression of motor neuron disease and correlate with anti-glioma immunity. Moreover, bone marrow transplantation experiments underscore the key role of the immune system in ALS4 neurodegeneration.

Join us as we discuss these breakthrough findings with Dr. Campisi and explore their potential implications for understanding ALS pathogenesis and identifying possible biomarkers for the disease state.

Keywords: ALS, ALS4, Senataxin gene, SETX, Immune system, CD8 T cells, Neurodegeneration, Dr. Campisi.

Campisi, L., Chizari, S., Ho, J.S.Y. et al. Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4. Nature (2022). https://doi.org/10.1038/s41586-022-04844-5