Mar 20, 2014

UCI Stem-Cell Pioneer Poised to Launch Clinical Trial for RP Patients

Eye On the Cure Research News

Dr. Henry Klassen’s progenitor-based therapy has the potential to rescue a variety of retinal cells — including rods, cones, retinal pigment epithelium and ganglion cells — and, therefore, may save vision in people with a wide range of conditions.

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Photo of Henry Klassen, M.D., Ph.D.

Henry Klassen, M.D., Ph.D.

Henry Klassen, M.D., Ph.D., is only about a year from launching a clinical trial for a stem cell treatment to rescue vision in people with retinitis pigmentosa (RP) and, potentially, other retinal diseases. At the Foundation's recent Orange County Innovation Symposium, the University of California (UC), Irvine clinician-researcher reported that he and his colleagues are in the midst of final lab studies with patient-grade cells. Once finished, they'll request authorization from the U.S. Food and Drug Administration to begin their human study.

But Dr. Klassen's 35-year research journey to this pivotal moment was by no means conventional, nor was it embraced by many of his peers.

"During medical school at the University of Pittsburgh in the late '80s, they thought I was crazy for getting a Ph.D. in addition to an M.D.," he says. "That's because, with a medical degree, there was nothing standing between me and an excellent income."

He received similar criticism when he went from Yale, where he did his residency, to Moorfields Eye Hospital in England for a post-graduate fellowship. He passed on becoming a high-paying retinal surgeon because "the need for doing more research was reinforced when I saw the retinal degeneration patients," he recalls. "The diagnosis was a grim message to have to deliver. I decided to concentrate on the research and come back to the clinic when I had something more to offer to patients."

It was in the lab of Ray Lund, Ph.D. — a leading cell-therapy innovator who's received Foundation funding — where Dr. Klassen first saw the potential for cell transplantation to restore vision. "When I got to Pittsburgh, I learned that Ray was doing retinal transplants and had showed that retinal grafts transplanted into the brain survived, and there was some integration," he says. "That really thrilled me, so I joined his lab."

Those early retinal graft experiments — before stem cells could be made into retinal cells — were technically difficult and tough to translate to humans. But they showed that transplanted retinal cells could connect to host neural tissue. Most important, they laid the groundwork for future retinal transplantation strategies, including those using stem cells.

In the 1990s, in collaborations with Dr. Lund and Michael Young, Ph.D., who was then at M.I.T., Dr. Klassen began making game-changing advancements in transplanting retinal cells into the eyes of rats with retinal degenerations. "As I'm looking through this microscope, I'm seeing something I never expected — a transplanted cell that could migrate through adult neural tissue and find its way to the right spot, park and start extending new connections into the host circuitry," he remembers. "It was amazing. It was the breakthrough I'd been looking for."

That was also about the time when he received a Career Development Award from the Foundation, to help advance his research. "I had seen a flier from the FFB when it was known as the RP Foundation. It was exciting to find an organization that was doing exactly what I wanted to do," says Dr. Klassen.

Today, stem cell research for retinal diseases is blossoming, with several clinical trials planned or underway. Dr. Lund's work led to the 2011 launch of Advanced Cell Technology's human trial of a stem-cell-derived therapy for people with age-related macular degeneration and Stargardt disease. With support from the Foundation, Dr. Young is helping the company ReNeuron prepare for a stem cell clinical trial for people with RP scheduled to begin by early 2015. Both ReNeuron's and ACT's therapies involve injections of cells underneath the retina to replace those cells lost to disease.

Dr. Klassen's forthcoming clinical study involves the injection of retinal progenitors — stem cells that have partially developed into retinal cells — into the patient's vitreous, where they'll release factors to preserve and rescue existing retinal tissue. He says that a benefit of his approach is that it doesn't involve a more invasive subretinal procedure, which would be required if lost cells were being replaced. Also, his progenitor-based therapy has the potential to rescue a variety of retinal cells — including rods, cones, retinal pigment epithelium and ganglion cells — and, therefore, may save vision in people with a wide range of conditions.

After decades in the field, Dr. Klassen acknowledges that reaching this promising juncture wasn't easy. "I have seen a lot of ups and downs with these technologies. It wasn't like somebody invented one thing in their garage and everything was solved," he says. "Finally, we are getting to the point where stem cells are poised to do something meaningful in the clinic."