Henry Klassen, the Stem Cell Scientist at UC Irvine Who’s Changing the Game in Retinitis Pigmentosa Treatment

By Jackie Ward

Imagine building your entire professional career around your favorite topic from the fourth grade. (By now, I would be an oversized horse jockey instead of a stem cell biologist.) Few people are fortunate enough to discover their life passion as young children; most of our childhood fixations fall by the wayside by early teenage-dom. Dr. Henry Klassen at the University of California, Irvine, is an exception. As a fourth-grader, Klassen suffered sunlight-induced headaches. Concerned that retinitis pigmentosa (RP), an inherited form of blindness, was to blame for these headaches, the local optometrist referred him to a regional ophthalmologist. Fortunately, his headaches were not caused by RP. However, this experience sparked a keen interest in the biology of the eye. Klassen subsequently wrote a report on the retina for his fourth grade class, unaware at the time that this project would be the first of many to come.

Klassen has both an M.D. and a Ph.D. — which means he has a penchant both for research and for treating patients. After finishing his medical fellowship at Moorfields Eye Hospital and Institute of Ophthalmology in London, Klassen immediately began searching for ways to translate his research findings into real treatments for people. He began exploring the use of stem cells as a way to treat people with retinal disease, eventually landing at UC Irvine in 2006.

RP is an inherited progressive form of retinal degeneration. If you recall from your high school biology class, the retina is a specialized tissue in the back of the eye containing light-sensing cells called cone and rod photoreceptors. These cones and rods are responsible for converting light rays into electrical signals that travel to the brain, resulting in the experience of sight. The rods are responsible for night vision and generally are located around the periphery of the retina. Cones are more centrally located and are responsible for color vision. Generally, the first symptom of RP is difficulty seeing at night, indicating rod degeneration. As more photoreceptors — both rods and cones — die, impaired night vision progresses to tunnel vision, and eventually complete blindness. RP is the most common form of inherited blindness, and affects populations worldwide. RP can be caused by mutations in more than 60 different genes.

In hopes of treating this devastating disease, Klassen has initiated a clinical trial at UC Irvine to test the effects of retinal progenitor cells in patients with RP. Retinal progenitor cells are stem cells whose development is strictly limited to the capacity to generate the retina. jCyte, Klassen’s spin-off company from UC Irvine, is sponsoring the trial with collaborators at the Gavin Herbert Eye Institute and the Retina-Vitreous Associates Medical Group. When an RP patient is selected for the clinical trial, Klassen and his jCyte co-founder, Dr. Jing Yang, prepare the cells and then hand-deliver them to the clinic. The cells have already undergone clinical manufacturing processes, so they are ready to go on relatively short notice. The cells are loaded in a syringe connected to a very thin needle, and then injected through the white of the eye into the large bowl of jelly inside the eyeball known as the vitreous cavity. The entire process is quick, simple, and relatively painless. Patients hang out in the clinic for a bit and then are released to go home.

Importantly, these cells are not directed specifically to the retina itself, but to the vitreal jelly surrounding the retina. At this point, it is not expected that they will replace the rods and cones that are dying. Instead, they can help by releasing tiny protective proteins, called cytokines, that support the healthy photoreceptors still present in the retina. This approach has already been tested in animal models, resulting not only in the presence of significantly more healthy photoreceptors when compared to untreated animals, but also preserved function in vision tests similar to those used in humans.

For now, Klassen’s trial is primarily focused on safety. One unique aspect is that the patients do not undergo immune suppression — “dampening” of the immune system in order to prevent the body’s rejection of the cell transplant. The only preparation a patient receives is numbing eye drops and a dose of antiseptic. As with any early Phase clinical trial, the goal is simply to ensure that the procedure is safe and tolerable to the patients. For many reasons, having two eyes here is a good thing. By injecting just one eye, the doctors are able to evaluate any adverse effects that might occur by comparing it directly to the untreated eye. So far, there have been 17 patients treated with no major safety concerns. By the end of the year, the goal is to enroll another 4 or more.

So what’s next? If data from the Phase 1/2a portion of the trial shows that the treatment is safe, Klassen will move on to a Phase 2b clinical trial to evaluate how well the treatment actually affects patients’ vision. This will likely involve a test of visual acuity — or sharpness of vision — in conjunction with the treatment. (Watch this video for more of the ins and outs of the clinical trial process.) So far, Dr. Klassen’s work has been supported by Early Translational and Disease Team grants from the California Institute for Regenerative Medicine (CIRM), the state stem cell agency. CIRM was created by Proposition 71, the California citizens’ initiative that authorized $3 billion for stem cell research and therapy development.

Klassen says that “CIRM has played a critical role in our rapid progress, and I don’t know if this would even have been possible without their support. One can imagine things still progressing along at a much slower pace, but that is not a formula for actual translational success.”

Klassen is still wary of the dreaded “Valley of Death” that cripples the progress of so many clinical trials. This is the transition from the academic research lab to the actual commercialization and delivery of the therapy, and can require billions of dollars. He is acutely aware of the challenges he’s already faced and what lies ahead. In his words: “It ain’t no disco.” jCyte is currently pursuing private investment as a way to help sustain the project through the remaining phases of clinical trials.

It’s fortunate for most of us that we move past our 4th grade interests (although we could have far more racecar drivers and ballerinas.) For Dr. Henry Klassen, however, his initial fascination seems to have panned out pretty well. He hopes his work will lead to the first treatment for patients with RP: something that 4th graders one day soon could include in their reports on the retina.