New breakthrough to prevent alterations in the cell degeneration process in the rare disease spinal muscular atrophy

Research conducted in Lleida has discovered a new link between intracellular calcium, signalling pathways and autophagy that represents a new advance in preventing alterations in the process of cell degeneration in spinal muscular atrophy (SMA), a minority disease affecting children. This finding allows further progress to be made in research into this rare disease and offers a useful strategy for developing new therapies to prevent the degeneration it causes.

The research, which has been published in the journal Cell Death Discovery, has been led by research groups from the University of Lleida and IRBLleida,  Neuronal Signalling Unit and Experimental Neuromuscular Pathology."Unfortunately, not all patients respond to current therapies for SMA, so we have to continue researching to find mechanisms to design new treatments," explained UdL professor of Medicine and head of the Neuronal Signalling Unit, Rosa Maria Soler Tatché.

Spinal Muscular Atrophy is a neuromuscular disease characterised by degeneration of motor neurons that appears in childhood. Motor neurons are a type of nerve cell in the spinal cord and lower part of the brain that control movement. The main cause of the disease is a change in the SMN1 gene, which is responsible for producing a protein that motor neurons need to be healthy and function properly. But when the SMN1 gene is missing or abnormal, there is not enough protein and this causes the motor neurons to degenerate. SMA affects 1 in 6,000 to 10,000 live births and is the most common cause of infant death of genetic origin.

The research has been conducted on mouse models and also on human samples. "Our results propose a link between calcium levels, intracellular survival pathways and autophagy, a cell maintenance mechanism, so that if we can regulate these alterations together, we can have an impact on neuronal degeneration," added Dr. Soler.

This work has been funded with grants from the Instituto de Salud Carlos III, PI20/00098 and co-funded by the European Union; Fundació La Marató TV3 (202005-30); Ministry of Science and Innovation/FEDER (grant number: PID2021-122785OB-I00), and the CERCA programme of the Generalitat de Catalunya. The research staff involved in the research also received grants from the Diputació de Lleida, AGAUR (INVESTIGO 2022 programme financed by the European Union, Next Generation EU grants and grants for the recruitment of pre-doctoral research staff in training, financed by the European Social Fund).

Article:
Sansa, A., Miralles, M.P., Beltran, M. et al. ERK MAPK signaling pathway inhibition as a potential target to prevent autophagy alterations in Spinal Muscular Atrophy motoneurons. Cell Death Discov. 9, 113 (2023). https://doi.org/10.1038/s41420-023-01409-x