MAPK inhibition to protect against spinal muscular atrophy
SMN protein deficiency has been linked to spinal muscular atrophy (SMA).
The authors carried out a chemical screen and identified p38 MAPK inhibition as a candidate suppressor of SMN-dependent cellular phenotypes. They also found that SMN deficiency leads to activation of p38 MAPK in both in vitro and in vivo models.
They also demonstrate that pharmacological treatment with the p38 MAPK inhibitor MW150 preserves SMA motor neurons and improves motor function in SMA mice, independent of changes in SMN levels.
In combinatorial therapy with SMN-inducing drugs, MW150-mediated neuroprotection further promotes synaptic rewiring and synergistically improves phenotypic outcomes.
Thus, the study identifies p38 MAPK pathway as a therapeutic target and MW150 as a neuroprotective drug for combination therapy in SMA.
https://www.embopress.org/doi/full/10.1038/s44321-025-00303-6
