Gene Therapy Works In Mice To Prevent Blindness That Strikes Boys

Writing in the August issue of Molecular Therapy, scientists fromthe UF Genetics Institute describe how they successfully used genetherapy in mice to treat retinoschisis, a rare genetic disorder that ispassed 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 devastatingresults. What happens is the retina actually begins to split in themiddle, causing loss of central vision - that's the vision that youneed to be able to read or walk around."

Scientists say the gene transfer method eventually could beapplied to many eye diseases caused by single gene defects, including ahost of retinal disorders.

Retinoschisis is usually first detected in boys between 5 and10 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 thevision and often leading to blindness in about 1 of every 5,000 boys.

UF researchers injected a healthy version of the human RS1gene to the sub-retinal space of the right eyes of 15-day-old malemice, which, like boys with the disease, don't have the healthy gene tomaintain the retina. In terms of disease development, the condition inthe mice was roughly equivalent to retinoschisis in a 10-year-old boy.

Six months later, researchers looked at the interior of theeyes with a laser ophthalmoscope and found cyst formation was clearlyevident in the untreated eyes, but the treated eyes appeared healthy.The eye's photoreceptor cells - the rods and cones that help the brainprocess light and color - were spared from the disease and theconnections between the layers of the retinas were intact.

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

The treatment has promising implications for other genetic eyediseases that involve the eye's ability to process light, includingretinitis pigmentosa, which affects about 200,000 people in the UnitedStates and is one of the most common inherited causes of blindness inpeople between the ages of 20 and 60.

"We've been very successful in curing a disease in mice thathas a direct copy in humans," said Hauswirth, who, in conjunction withUF, has interest in a biotechnology company that may seek to marketsome of the research technology. "It may take two to five years beforewe 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 formalevidence for safety that will allow us to get treatment into theclinic."

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

The Foundation Fighting Blindness, the National Institutes ofHealth and the Macula Vision Research Foundation supported theresearch.

"We now have proof of principle that gene therapy can basicallyprevent retinoschisis," said Stephen Rose, Ph.D., chief researchofficer for the Maryland-based Foundation Fighting Blindness."Furthermore, this therapy apparently demonstrates that even if diseasehas begun, there is a healing that takes place. That raises hope forsuffering patients that we may be able to offer something that canimprove the quality of their lives."