Gene therapy works in mice to prevent blindness that strikes boys

GAINESVILLE, Fla. — University of Florida scientists used a healthy human gene to prevent blindness in mice with a form of an incurable eye disease that strikes boys.

Writing in the August issue of Molecular Therapy, scientists from the UF Genetics Institute describe how they successfully used gene therapy in mice to treat retinoschisis, a rare genetic disorder that is passed from mothers, who retain their sight, to their sons.

“Currently there is no treatment,” said William Hauswirth, Ph.D., the Rybaczki-Bullard professor of ophthalmic molecular genetics. “These children lose their sight gradually, often with devastating results. What happens is the retina actually begins to split in the middle, causing loss of central vision — that’s the vision that you need to be able to read or walk around.”

Scientists say the gene transfer method eventually could be applied to many eye diseases caused by single gene defects, including a host of retinal disorders.

Retinoschisis is usually first detected in boys between 5 and 10 years of age when their vision problems cause reading difficulties. In a healthy eye, retinal cells secrete a protein called retinoschisin, or RS1, which acts like glue to connect the layers of the retina. Without it, the layers separate and tiny cysts form, devastating the vision and often leading to blindness in about 1 of every 5,000 boys.

UF researchers injected a healthy version of the human RS1 gene to the sub-retinal space of the right eyes of 15-day-old male mice, which, like boys with the disease, don’t have the healthy gene to maintain the retina. In terms of disease development, the condition in the mice was roughly equivalent to retinoschisis in a 10-year-old boy.

Six months later, researchers looked at the interior of the eyes with a laser ophthalmoscope and found cyst formation was clearly evident in the untreated eyes, but the treated eyes appeared healthy. The eye’s photoreceptor cells — the rods and cones that help the brain process light and color — were spared from the disease and the connections between the layers of the retinas were intact.

In addition, the protein appears capable of moving within the retina to its target sites and the beneficial changes appear to be long lasting, researchers said. Especially encouraging were signs the treatment may be able to repair retinal damage.

The treatment has promising implications for other genetic eye diseases that involve the eye’s ability to process light, including retinitis pigmentosa, which affects about 200,000 people in the United States and is one of the most common inherited causes of blindness in people between the ages of 20 and 60.

“We’ve been very successful in curing a disease in mice that has a direct copy in humans,” said Hauswirth, who, in conjunction with UF, has interest in a biotechnology company that may seek to market some of the research technology. “It may take two to five years before we try this in human patients because of the need for safety studies, but we feel based on success so far, we will be able to provide formal evidence for safety that will allow us to get treatment into the clinic.”

UF researchers worked with Bernhard Weber, Ph.D., at the Institute of Human Genetics in Regensburg, Germany, and Robert Molday, Ph.D., director of the Center for Macular Research at the University of British Columbia in Vancouver.

The Foundation Fighting Blindness, the National Institutes of Health and the Macula Vision Research Foundation supported the research.

“We now have proof of principle that gene therapy can basically prevent retinoschisis,” said Stephen Rose, Ph.D., chief research officer for the Maryland-based Foundation Fighting Blindness. “Furthermore, this therapy apparently demonstrates that even if disease has begun, there is a healing that takes place. That raises hope for suffering patients that we may be able to offer something that can improve the quality of their lives.”