Bascom Palmer Study Shows Gene Therapy Safe for Rare Eye Disease

Long-term results of the first-ever gene therapy clinical trial in the U.S. for a mitochondrial disease, Leber Hereditary Optic Neuropathy (LHON), initiated in 2014, showed low and medium doses improved visual acuity in most patients when treated within one year of onset of visual loss. The study, conducted at Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, involved 14 patients with LHON, a disorder caused by genetic defects inside mitochondria, the energy factories inside cells, that results in rapid, permanent and bilateral loss of vision in people of all ages, but primarily men ages 20-40.

“These long-term results from the study are very encouraging,” said John Guy, M.D., the principal investigator of the study. Through this trial, patients with visual loss from LHON received a single-unilateral dose injection of a normal version of their mutated mitochondrial gene into the eye. Acuity began to improve within one month of treatment and continued to do so as long as 18 months later. Average improvement was 0.96 logmar (0.1 logmar equals 5 letters or 1 line on the eye chart) at 18 months of follow-up relative to 0.21 logmar reported in the prior natural history study of those with this mutation. A patient who was legally blind and the first acute case to receive the gene therapy is able to drive again. Still, those who were legally blind for more than two years saw no changes in vision suggesting a window for initiation of treatment may be key.

In addition, OCT measurements of the retinal nerve fibers showed treatment halted the characteristic degeneration of the optic nerve that continued to deteriorate in untreated eyes at 12 months of follow-up. Adverse effects of treatment were mild and included transient inflammation of the eye that was asymptomatic and resolved on its own. These results pave the way for the next phase of the clinical trial for injection of the highest dose that is 5 and 20 times more concentrated than the low and medium doses described so far.

“John Guy is the world’s foremost expert on research and pioneering gene therapy techniques for LHON,” said Eduardo C. Alfonso, M.D., director and chair of Bascom Palmer. “I am confident this landmark article on the safety of gene therapy will be beneficial to a wide range of other conditions caused by mutations in mitochondrial DNA and will help to restore vision for those affected by serious eye conditions.”

Guy, the Rodgers Research Chair in Ophthalmology at Bascom Palmer, is funded through an approximately $8 million cooperative agreement from the National Eye Institute (NEI) (U10 EY023558). The preclinical research leading to the approval for the study by the Food and Drug Administration was funded by another award (R24 EY018600) through NEI’s Translational Research Program on Therapy for Visual Disorders.

The article was accepted in Ophthalmology under the title “Gene Therapy for Leber Hereditary Optic Neuropathy.” Bascom Palmer scientist and biostatistician William J. Feuer, M.S., was co-author of the study and provided the key analyses of the data.

In addition to Guy and Feuer, study co-investigators include Janet L. Davis, M.D.; Vittorio Porciatti, Ph.D.; Phillip J. Gonzalez, CCRP; Rajeshwari D. Koilkonda, Ph.D.; Huijun Yuan, Ph.D.; and Bryon Lam, M.D., of Bascom Palmer Eye Institute; and William W. Hauswirth, Ph.D., University of Florida College of Medicine.

About Bascom Palmer Eye Institute
Bascom Palmer Eye Institute is ranked the nation’s best in ophthalmology by U.S. News & World Report, an honor it has received for 13 consecutive years. In addition to its international reputation as one of the premier providers of eye care in the world, Bascom Palmer is the largest ophthalmic care, research and educational facility in the southeastern United States. Each year, more than 250,000 patients are treated with nearly every ophthalmic condition and more than 18,000 surgeries are performed. With five patient care facilities in Florida (Miami, Palm Beach Gardens, Naples, Plantation, and The Lennar Foundation Medical Center in Coral Gables), the Institute serves as the Department of Ophthalmology for the University of Miami Miller School of Medicine. Bascom Palmer faculty members also staff the Miami and West Palm Beach Veterans Affairs Medical Centers, Jackson Memorial Hospital and Miami Children’s Hospital.

News Archives

Office of the Dean

A message from the dean

Physician News

Read Med News


Read e-Update