Gene Therapy for Blindness

The Science Behind This Breakthrough

Eight years ago, The Children’s Hospital of Philadelphia (CHOP) established the Center for Cellular and Molecular Therapeutics with the goal of developing cell and gene therapies for a wide range of serious diseases.

It was an ambitious step – and a risky one.

Other teams had embarked on gene therapy research with very high expectations – and ended up with little to show for it. Federal funding for such work was extremely hard to come by, and pharmaceutical companies simply weren’t interested in investing in something so new and unproven. There were no licensed gene therapy products in use in the Western world.

But leaders at The Children’s Hospital of Philadelphia believed that a major breakthrough was possible. “The Hospital’s senior leadership felt strongly that this technology, if properly developed, could have a major impact on the inherited diseases that form a very significant part of the patient population at all children’s hospitals,” says Katherine A. High, MD, the center’s director.

Soon, the Hospital began laying the groundwork for a gene therapy breakthrough, building a facility to manufacture the vector used to deliver the therapeutic genes and recruiting top experts in the field to join High’s team.

Just a few years later, the team began enrolling patients in a gene therapy study for Leber congenital amaurosis (LCA), a rare form of inherited blindness.


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The Gift of Sight

The study involved five children and seven adults with LCA, all of whom reported improved vision in dimly lit environments in the treated eye. (In the first part of the study, researchers treated only one of each patient’s eyes – the one with worse vision – out of an abundance of caution.) Each also showed improvement in measures of the pupil’s response to light and in vision tests. Six patients improved enough to no longer be classified as legally blind, with the greatest improvements occurring in the children – a testament to the value of early intervention for progressive diseases like LCA. Results of the study were published in the medical journal The Lancet in October 2009.

“If once in your career you’re involved in developing a therapy that really makes a difference in people’s lives, that’s very exciting. It’s all you ever really hope for.”
Katherine A. High, MD, Director, Center for Cellular and Molecular Therapeutics

Another Step Forward

In the next phase of the research, three adult patients from the first study received gene therapy in the other eye. All three showed further improvements in vision after the second eye was treated, and neither the first treatment nor the second treatment triggered an immune reaction that cancelled the benefits of the inserted genes, as has occurred in human trials of gene therapy for other diseases. Results of the study were published in the medical journal Science Translational Medicine in February 2012.

A New Frontier

Eleven patients with LCA have now received gene therapy in both eyes, and High and her team are conducting additional studies with the goal of getting the therapy licensed so it can be offered to even more patients. High’s team is also working on gene therapy for Huntington’s disease, hemophilia and another form of congenital blindness.

It’s an exciting turnaround for a field once fraught with controversy – and a testament to just how much the most talented scientists can do when they have the resources they need.

How Gene Therapy for LCA Works

Using DNA, scientists create a functioning gene to replace the faulty one in the retina.

Then they place the new gene inside a little “coat” made up of viral proteins (known as a vector). The vector is a highly ordered set of proteins, copied from a virus, that functions to deliver a gene to a target cell.

Scientists add in the new gene by injecting it directly into the eye through a thin needle (1) connected to a syringe, with the help of a light probe (2). The new gene (3) enters the cell nucleus (4), where it makes the healthy enzymes (5) required to see.

Availability of Gene Therapy for LCA

Gene therapy for Leber congenital amaurosis (LCA) is experimental and is not yet approved by the United States Food and Drug Administration. It is only available through enrollment on a clinical trial. Patients must meet specific eligibility criteria to enroll.

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