Leber Congenital Amaurosis Research Advances
Recent developments in research on Leber congenital amaurosis
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. FFB 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 Mutations) 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. Foundation-funded Investigators from the Universities of Pennsylvania and Florida demonstrated efficacy for gene therapy in two mouse models of LCA1 — one rich in cones, the other rich in rods. Based on an adeno-associated virus, the treatment provided profound improvement in vision for the mice.
Gene Therapy for LCA6 (RPGRIP1 Mutations)
A research team from Massachusetts Eye and Ear Infirmary 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 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.
ProQR Reports Vision Improvements in Its LCA10 (CEP290) Therapy Clinical Trial
ProQR, a biotech company in the Netherlands, has reported vision improvements for patient in a Phase 1/2 clinical trial for QR-110, a therapy for people with Leber congenital amaurosis 10 (LCA10), which is caused by the p.Cys998X mutation in the CEP290 gene. The mutation is estimated to affect about 2,000 people in the Western world. The company launched a Phase 2/3 trial for QR-110. The treatment, known as an antisense oligonucleotide, is delivered through an injection into the vitreous, the gel-like substance in the middle of the eye. It works like a piece of genetic tape to mask the mutation.
Vision Improvements Reported in Two LCA 10 Patients in Phase 1/2 Clinical Trial for Editas' CRISPR/CAS9 Treatment
Editas reported that two of three participants in the mid-dose group of Editas’ BRILLIANCE Phase 1/2 clinical trial for its LCA 10 CRISPR/Cas9 treatment showed improvements in vision. Known as EDIT-101, the emerging gene-editing therapy is the first of its kind to be administered directly to the human body.
One participant in the BRILLIANCE trial had improvements in best corrected visual acuity (BCVA, the ability to read lines on an eye chart) sustained for six months and in the ability to navigate a mobility course at the sixth month after treatment. Also, the participant showed a positive trend in retinal sensitivity (as measured by a full field stimulus threshold test or FST).
RD Fund Launches Opus Genetics to Advance Gene Therapies for Inherited Reginal Diseases
The Retinal Degeneration Fund (RD Fund), the venture philanthropy arm of the Foundation Fighting Blindness has launched Opus Genetics, a patient-focused gene therapy company targeting inherited retinal diseases. The company’s lead programs are licensed from the University of Pennsylvania and will focus on treatments to address mutations in genes that cause different forms of Leber congenital amaurosis (LCA). Opus’s lead program, 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. The company’s second program, OPGx-002, will focus on restoring protein expression and halting functional deterioration in patients with retinal dystrophy caused by mutations in the RDH12 gene (LCA13), which affects one in 288,000 people.