Leber Congenital Amaurosis Research Advances

FDA APPROVES SPARK’S VISION-RESTORING GENE THERAPY

Spark Therapeutics’ vision-restoring RPE65 gene therapy has received marketing approval from the U.S. Food and Drug Administration, becoming the first gene therapy to gain regulatory approval in the U.S. for the eye or any inherited condition. Known as LUXTURNA™ (voretigene neparvovec), the gene therapy restored vision in a clinical trial for people between the ages of 4 and 44 with Leber congenital amaurosis (LCA) caused by mutations in the gene RPE65. Study participants with severe vision loss reported putting away their navigational canes, seeing stars, being able to read, and recognizing faces of loved ones. Vision restoration has persisted for at least three years. The treatment is also designed to work for people with retinitis pigmentosa (RP) caused by RPE65 mutations. The Foundation invested about $10 million in more than a decade of lab research that made possible the RPE65 gene therapy clinical trial at the Children’s Hospital of Philadelphia (CHOP).

GENE THERAPY FOR LCA1 (GUCY2D) IMPROVES VISION IN CLINICAL TRIAL

With funding from the Foundation, Atsena is conducting a Phase 1/2 clinical trial for a gene therapy for people with LCA caused by mutations in the gene GUCY2D. The nine patients in the trial receiving the highest dose had improvements in retinal sensitivity and their ability to navigate a low-luminance mobility course. The treatment was developed by Shannon Boye, PhD, at the University of Florida.

THÉA ACQUIRES PROQR’S EMERGING RNA THERAPY FOR LCA10 (CEP290)

Théa has acquired ProQR’s RNA therapy sepofarsen for people with Leber congenital amaurosis 10 (LCA10) caused by the mutation p.Cys998X in the gene CEP290. Previously, ProQR reported that its Phase 2/3 ILLUMINATE clinical trial of sepofarsen did not meet its primary endpoint though some patients did show vision improvements. Théa plans further clinical development of sepofarsen.

OPUS GENETICS LAUNCHES LCA5 GENE THERAPY CLINICAL TRIAL

Opus Genetics, a patient-focused gene therapy company launched by the Foundation, has moved its lead program, OPGx-001, into a Phase 1/2 clinical trial at the University of Pennsylvania. OPGx-001 is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein. LCA5 is one of the most severe forms of LCA, affecting approximately one in 1.7 million people.

GENE THERAPY FOR LCA6 (RPGRIP1 MUTATIONS)

Odylia is developing a gene therapy based on an adeno-associated virus for LCA caused by RPGRIP1 mutations. Future plans include generating a clinical-grade gene-therapy vector for toxicology studies, and ultimately, a clinical trial. Dr. Eric Pierce’s clinic at Mass Eye and Ear has also identified seven families with RPGRIP1 mutations. An earlier study showed that gene therapy rescued degenerating rods and cones in a mouse model of the condition.

SEPTEMBER 2023