Cure for Hereditary Blindness in Sight

By Paddy Kamen

Discovering that your child has an incurable eye disease can be devastating, and any good parent would be moved to action. But to go from your own child’s problem to working on a cure for millions is indeed extraordinary.

Ocular Albinism (OA) is an untreatable inherited disorder in which the eyes are deficient in melanin and pigment, resulting in reduced visual acuity, nystagmus and sensitivity to sunlight. “When we discovered that our infant son Chase had this disorder we hoped that it could be ameliorated with special lenses, surgery or drugs,” says Sam Hardage. “But when we realized that there was nothing that could be done in terms of treatment, we thought we’d find the scientists working towards a cure and help them out. You’d think that with six billion people on the planet, some researchers would be working on genetically caused retinal disorders. But no one was.”

The Hardages next started looking for researchers who would be interested in working on OA. “We found some Italian post-doctoral researchers at Baylor University and told them we would fund the research if they would try to find the gene responsible for OA,” explains Hardage. “By this time we figured that the only solutions would be gene therapy or stem cell research.”

It made sense to start a foundation, and so in 1991 the Hardages created Vision of Children (VOC), a non-profit genetic research and support organization for visually impaired individuals and their families. The research mandate grew to cover a group of 25 hereditary vision disorders including retinitis pigmentosa, Ushers syndrome and Leber’s congenital amaurosis. Today VOC supports 23 researchers at 12 institutions worldwide.

VOC supports families in several ways, as Hardage explains: “We wanted to let people know that someone was working to help find a cure for these diseases. We also wanted parents and kids to know that they were not alone, so we created a family network.”

Almost 500 families from around the globe belong to the Family Network. “We personally connect parents to other parents who have a child in the same age range and hopefully same gender,” explains Michelle Pius, development director for VOC. “We also try to connect families within the same geographic region. The network enables them to find support and to see what challenges they may be facing as their child grows older.”

The Family Network is fostered by Internet connections, phone calls and face-to-face meetings where distance is not an issue.

Families and individuals are also welcome at the biennial research symposium sponsored by VOC, where scientists working on the issues share study results in addition to work-in-progress. In fact, in contrast to most symposia, where published or pre-publication research results are the only kind of work shared, VOC requires that participating researchers be ready and willing to share their ideas, methods and preliminary findings.

“It was quite difficult at first to convince presenters to share their work before completion,” notes Hardage. “But once they try it they find it makes a tremendous learning environment. We encourage a collaborative, non-proprietary attitude. During one symposium in New York City (at the invitation of the New York Academy of Sciences) several researchers from two major universities became interested in one of the subjects discussed and decided to collaborate on a joint project which is now in its fourth year. It’s really exciting to see things like that happen. The idea is to kindle the process of discovery, speed up the development of solutions and push the envelope so that kids who don’t see clearly, can.”

The seventh Vision of Children's World Symposium on Genetic Vision Disorders was held in San Diego on May 30th and June 1st, 2008. Top researchers from around the world joined with vision care providers and families to discuss the latest discoveries and research efforts on OA and related conditions. Institutions represented included the Jules Stein Eye Institute, Columbia University, Telethon Institute of Genetics and Medicine and the National Eye Institute.

Recently completed and highly successful gene therapy trials were a great boost to everyone’s morale at the symposia. The world’s first clinical trials to test a revolutionary gene therapy treatment for Leber’s congenital amaurosis (LCA) were completed at the NIHR Biomedical Research Centre in Britain in the spring of 2008, with results published in the New England Journal of Medicine.

LCA is a group of inherited blinding diseases that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness during a patient’s twenties or thirties. The technique used in the trial involved inserting healthy copies of the missing RPE65 gene into the cells of the retina to help them function normally. This involved an operation which delivered the normal genes to the retina, using a harmless virus or ‘vector’ to carry the gene into the cells.

The operation benefitted all three subjects, with one realizing a significant improvement in his night vision. This was demonstrated by his ability to negotiate a specially constructed simulation of a night-time street scene. Before the operation he completed the task slowly and made several mistakes, but following the surgery he was able to navigate quickly and without mistakes. The researchers believe the operation’s success for this particular patient could be because his disease had not progressed to the same extent as the others. The team has already begun to trial the technique in younger patients, where they hope to achieve even better results.

The British results were subsequently replicated with even better outcomes at the Children’s Hospital of Philadelphia, where they were able to restore vision in three young adults with LCA. Although the patients have not achieved normal eyesight (their vision improved from detecting hand movements to reading lines on an eye chart), the preliminary results set the stage for further studies and innovative treatments for this and possibly other retinal diseases.

A third trial at the University of Florida achieved similar results.

Before the human trials began, the same naturally occurring form of congenital blindness had been reversed in dogs. The VOC’s persistent push for trials of gene therapy in human subjects was one of the factors that led to these astounding results. “This is a major success and has already spawned all kinds of efforts and will change the face of medicine,” notes Hardage.

It is Hardage’s personal drive to never take no for an answer that continues to spark innovation and transformation in the lives of individuals living with these debilitating disorders. Upon noticing that his son Chase had to assume an unnatural body position in order to read the screen on his computer, Hardage began researching alternatives and found that the solution lay in dental office technology. He modified the heavy duty ‘arm’ equipment that holds a tray with the dentist’s tools so that it could support an extra-large computer monitor, which was then brought close to Chase’s face while he was sitting in a normal, upright position. “This made a huge difference in his life, so we started having flat screens and arms made for this purpose and began giving them to school computer labs and people who cannot afford them. We’ve given hundreds of these away as gifts and it’s great that the kids who get to use them are typically the most disadvantaged in a school. It’s a boost to their self-esteem to be the ones with the high tech system. And we’ve noticed that our gift often serves as an impetus for the school to update the computer equipment for the other kids as well.”

VOC is housed in Hardage’s corporate offices in San Diego, California, where two full-time and one part-time staff work amongst employees of The Hardage Group, a corporation which owns and operates hotels in eleven states. The corporation pays employee salaries and covers the cost of administering the foundation. Research is typically co-funded by VOC and other organizations and the foundation gladly accepts donations to foster its many projects. For further information about VOC, visit their website at: www.visionofchildren.org.