Harvard Team Report One-Time Base Editing Treatment for Motor Neuron Disease in Mice

Using base editing, a team led by Harvard University scientists has treated spinal muscular atrophy (SMA) in mice, opening the door to a potential one-time treatment for the progressive motor neuron disease in humans. SMA is caused by homozygous loss or mutation of the essential survival motor neuron 1 (SMN1) gene, which encodes a protein called SMN. Approved therapies for the condition can increase SMN levels, but don't fix the underlying problem, require repeat dosing, and many wane in effectiveness. In a study appearing in Science this week, the researchers focused on SMN2, a gene closely related to SMN1 that harbors a mutation preventing it from regulating the SMN protein. They developed base editors to modify SMN2 into an active form and administered them to mouse models of SMA, bringing the animals' SMN levels to normal while improving their motor function and extending their lifespans with a single treatment. Importantly, the intervention did not alter endogenous regulatory mechanisms. "As such, a future base editing therapeutic approach could offer substantial benefits over existing SMA therapies," the study's authors write.