Recent Publication Highlights Gene Editing Breakthrough for Alternating Hemiplegia of Childhood (AHC)

In a significant study published in Cell, researchers from the Broad Institute and the Jackson Laboratory have unveiled a groundbreaking application of prime editing technology. Their work successfully corrected the genetic causes of Alternating Hemiplegia of Childhood (AHC) in a mouse model, a rare and severe neurodevelopmental disorder.

AHC symptoms, including paralysis attacks, muscle contractions, and seizures, typically emerge months after birth. With no current treatments, affected children face progressive muscle loss, developmental delays, and cognitive impairments.

Precision Gene Editing Offers Hope: Led by David Liu, the team specifically targeted five common mutations in the ATP1A3 gene, responsible for up to 70% of AHC cases. Utilizing prime editing – a highly precise genetic engineering technique derived from CRISPR-Cas9 that avoids harmful double-stranded DNA breaks – they first demonstrated successful in vitro correction in patient-derived stem cells.

Promising In Vivo Results: The researchers then delivered the prime editing system into the brains of postnatal mice, using an FDA-approved AAV9 viral vector. A single injection yielded remarkable results:

• High editing efficiency: Up to 85% correction of the target mutations.
• Significant symptom improvement: Treated mice exhibited better survival, fewer and less severe attacks, and restored motor coordination, mirroring healthy mice. As co-author Alexander Sousa noted, “Now we know you can [intervene after birth].”

This breakthrough offers compelling hope for a one-time therapy for AHC in humans, potentially through less invasive delivery methods in the future. Co-author Cathleen Lutz underscored the achievement, stating, “This level of editing efficiency in the brain is really quite remarkable.” The study’s implications extend beyond AHC, holding immense potential for correcting other ATP1A3 mutations and various neurodevelopmental disorders, opening doors to treat conditions long considered intractable.