Innovative Gene-Editing Technique Offers Hope for Childhood Vascular Disease Treatment

Researchers from Mass General Brigham have developed a groundbreaking gene-editing technology aimed at treating multisystemic smooth muscle dysfunction syndrome (MSMDS), a rare and often fatal condition in children characterized by stroke, aortic dissection, and neurodegeneration. Currently, there are no effective treatments or cures for MSMDS. The new approach involves a specially designed CRISPR-Cas9-based base editor that targets a specific mutation in the ACTA2 gene, which encodes the smooth muscle actin protein. This mutation is the primary cause of MSMDS.

In preclinical experiments using mouse models, the bespoke base editor demonstrated a significant extension of survival—up to four times longer than untreated mice—and improved vascular and neurological health. The innovative therapy employs a genome editing tool created by fusing a CRISPR-Cas9 protein with a DNA-modifying enzyme, guided precisely to correct the mutation. To optimize targeting and minimize off-target effects, researchers engineered new versions of the base editor with custom-made Cas9 enzymes. The delivery system was tailored to target smooth muscle cells in blood vessels, making this approach not only precise but also specific to the affected tissues.

Encouraged by these promising results, the team has initiated discussions with the U.S. Food and Drug Administration (FDA) to explore clinical trial options. The research has been recognized for its potential to transform treatments for vascular diseases, and the team envisions that this technology could eventually contribute to cures for other conditions involving vascular abnormalities, such as Marfan syndrome, Loeys-Dietz syndrome, Moyamoya disease, and even common cardiovascular issues like atherosclerosis.

This pioneering work highlights the potential of advanced genome editing techniques to address unmet medical needs in pediatric vascular diseases, paving the way for new therapeutic strategies that could save countless lives in the future.