Bascom Palmer announces LHON breakthrough

Miami-A Bascom Palmer Eye Institute (BPEI) research team has pioneered a novel technology treatment for Leber Hereditary Optic Neuropathy (LHON).

The team-led by John Guy, MD, professor of ophthalmology at BPEI, University of Miami Miller School of Medicine-recently advanced their research significantly by demonstrating that the vector (adeno-associated virus [AAV]) coupled with the ND4 gene was made human grade expressed in the ex vivo human eye and was proven safe in experimental models that are closest to the human eye, suggesting possible progression to a clinical trial.

These latest findings can be found in the Jan. 23 online edition of the Journal of American Medical Association Ophthalmology.

Funding for a clinical trial, which would allow injection of therapeutic genes into patients who have visual loss from mitochondrial disease, is currently being sought from governmental and other appropriate sources.

Dr. Guy’s preliminary research was funded in 2007 by National Institutes of Health and National Eye Institute grants, totaling $6.1 million.

It has been found that mutations in the mitochondria cause LHON. Currently, there is no treatment for this or any other disease caused by mutated mitochondrial DNA. However, Dr. Guy and his team previously modified a virus and used it to introduce healthy genes into the mitochondria to correct the genetic defect.

“In research conducted in 2012, we proved that it is both safe and effective to replace mutated genes with healthy ones, and that doing so prevents deterioration of the retinal cells that form from the optic nerve,” Dr. Guy said. “This research demonstrated that when efficiently introduced into mitochondria, normal DNA can correct a biochemical defect in cellular energy production and restore visual function.”

While many different experiential approaches have been proposed, development of a clinically effective therapy has been elusive.

“A wide range of other factors, including aging, cancer, and Parkinson’s disease, are also caused by mutations in the mitochondria,” he said. “This new approach shows the vast potential for genetic-therapy applications, while helping to address a significant cause of blindness.”

In Dr. Guy’s research, the healthy genes were delivered into the mitochondria via an innovative viral delivery system. Specifically, Dr. Guy redirected the AAV to the mitochondria rather than to its typical target-the nucleus-where most genes are housed within the cell. He did so using a mitochondrial-targeting sequence, a peptide chain that directs the transport of a protein. This permitted the replacement of the defective mitochondrial gene with a healthy one, which then restored energy production to the affected ocular cells.

“Other research studies have shown that LHON patients who have lost their vision still have approximately half their retinal cells remain,” Dr. Guy said. “This finding suggests that if you can restore the functioning of those cells through gene therapy, those patients could see again.

“We trust that the discovering of this vector (AAV with the ND4 gene) will serve as an important impetus for an eventual cure for the blinding disease LHON,” he said.

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