CRISPR trial for inherited blindness underway

Editas Medicine and Allergan are teaming up to conduct the first human trial of a CRISPR gene-editing therapy for inherited blindness. The phase 1/2 trial will test a single subretinal injection of AGN-151587, also called EDIT-101, in 18 patients with Leber congenital amaurosis 10.

Investigators plan to administer low, medium and high doses of the drug in children, and medium and high doses in teens. Although primarily designed to assess the drug’s toxicity and adverse events, the trial will also track changes in mobility, dark adapted visual sensitivity, contrast sensitivity, macular sensitivity, color vision, gaze tracking and quality of life.

Similar to the gene therapy Luxturna, EDIT-101 is delivered to retinal cells via an adeno-associated virus. But whereas Luxturna swaps out defective copies of the RPE65 gene—a major cause of Leber congenital amaurosis—for a functional version, the experimental therapy targets a much larger gene called CEP290 that cannot fit on a viral vector.

Instead of delivering a correct copy of CEP290, EDIT-101 delivers editing tools that home in on and correct a small typo called IVS26. The point mutation is thought to interfere with hair-like projections called cilia on the surface of photoreceptor cells.

The trial is set to begin this fall at Bascom Palmer Eye Institute, Massachusetts Eye and Ear Infirmary, W.K. Kellogg Eye Center and Casey Eye Institute. Preliminary safety and efficacy findings are expected next year.