Canadian Team to Conduct Clinical Trial for Choroideremia Gene Therapy

November 11, 2013

The Alberta Ocular Gene Therapy Team, at the University of Alberta in Edmonton, is planning to launch a Phase I human study of a gene therapy for choroideremia in the first half of 2014. The 12-person trial will be the first-ever in Canada for an inherited retinal-disease gene therapy. According to Ian MacDonald, M.D., who leads the team with Tania Bubela, J.D., Ph.D., the long-range plan is to conduct additional studies for other retinal conditions, including Stargardt disease and Usher syndrome type 1B.

“Our immediate goal is choroideremia, but we are looking to establish a center of excellence for ocular gene therapies to treat other inherited forms of vision loss, including conditions that affect the cornea,” says Dr. MacDonald. “Once we clear the regulatory hurdles for choroideremia, it will be easier for us and others to undertake the same process for other diseases.”

He adds that choroideremia is particularly amenable to gene therapy, because it begins as a biochemical disorder. If a patient can be treated early in the course of disease, when he or she is a child or young adult, the biochemical defect can be corrected, thereby preventing retinal degeneration and vision loss.

Only Canadian citizens will be able to participate in the forthcoming clinical trial. But if the treatment is ultimately approved by Health Canada, a regulatory agency similar to the U.S. Food and Drug Administration, it should be available to people traveling to Canada from the United States and other countries, say Dr. MacDonald.

“I have many patients who come to see me from the U.S., and I’d like to help them, too,” he adds. “We don’t see the 49th parallel as a barrier to getting treatments to those who need them.”

Two other choroideremia gene therapy development efforts are also underway. A Phase I/II clinical trial was launched in 2011 at the John Radcliffe Hospital, Oxford University, in the United Kingdom. Also, Jean Bennett, M.D., Ph.D., at The Children’s Hospital of Philadelphia, is planning to begin a human study in 2014.

“Having more than one gene therapy trial for the condition is important, because we each take a slightly different approach,” says Stephanie Chan, M.S., a certified genetic counselor and the choroideremia study coordinator. “With all of us going after the disease, the chances of success are greater. And the clock is always ticking for these patients.”

Chartered with advancing emerging genetic treatments into clinical trials, the Alberta Ocular Gene Therapy Team is comprised of a dozen members with varying expertise, including ophthalmology, pharmacology, medical genetics, physiology, ethics and health policy.

“The intent is to keep it multidisciplinary and multi-institutional,” says Georgie Jarvis, B.A., a certified clinical research professional and project manager of the team. “We even span institutions with an investigator from Northwestern University in the United States.”

Ms. Jarvis adds that the University of Alberta is developing a facility that follows good manufacturing practices — also known as GMP — for making gene therapies that meet quality and safety standards for study in humans.

Funding for the Canadian choroideremia gene therapy trial comes from a number of sources, including: the Canadian Institutes for Health Research, the country’s federal agency for research funding; Alberta Innovates - Health Solutions, an Alberta-based research funding organization; and the non-profits Canada Foundation for Innovation, Foundation Fighting Blindness (Canada) and the Choroideremia Research Foundation Canada.

The Foundation Fighting Blindness (U.S.) provided nearly two decades of funding for lab studies that helped make all three choroideremia clinical trials possible. Much of that support went to Miguel Seabra, Ph.D., University College London, who helped determine the function of the choroideremia gene, created a mouse model of the condition and developed an early version of the gene therapy in the lab.

From 2001-07, the Foundation Fighting Blindness (U.S.) also supported Dr. MacDonald’s research to better understand the genetics and visual consequences of choroideremia.

“Choroideremia gene therapy is a great example of how important collaboration is in moving research forward,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness (U.S.). “Fighting blindness is a global enterprise, and we are delighted by the progress it’s brought to bear in overcoming choroideremia and the entire spectrum of retinal degenerative diseases.”