May 3, 2016

ARVO 2016: What Does It Take to Develop a Stem-Cell Therapy for the Retina?

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There are innumerable considerations for researchers developing therapies.

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Photo of Drs. Jeffrey Stern and Sally Temple attending ARVO 2016 in Seattle.

Drs. Jeffrey Stern and Sally Temple attending ARVO 2016 in Seattle.

The effort to restore vision lost to retinal diseases using stem cells can sound so tantalizing simple. The researcher gets some stem cells, turns them into retinal cells, puts them in the patient’s retina to replace lost cells and—voila!—the patient can see again.

But the reality is, such a procedure can be mind-blowingly complex, and there is no one-size-fits-all therapy for people with conditions such as age-related macular degeneration (AMD) or retinitis pigmentosa. There are innumerable considerations for researchers developing therapies. Here are just a few:

  • What type of stem cells should be used? Those taken from blastocysts (stem cells often referred to as embryonic) or those derived from patients’ skin or blood (induced pluripotent stem cells)? Blastocysts require less manipulation than induced, but can raise ethical concerns for some people.
  • At what stage of development should the cells be transplanted into the eye? When they are fully mature or partially developed? The latter may have a better opportunity to integrate into the retina, but also may turn into an unwanted type of cells and compromise the safety of the patient.
  • Do you inject them as a bolus (i.e., a ball of liquid) and give them an opportunity to naturally migrate to where they’re needed? Or do you put them on a supporting scaffold, to keep them properly oriented, and perhaps increase their chances for survival?
  • Do you need to suppress the patient’s immune system? The eye is potentially protected from immune insults by the blood-retina barrier on the outside of the retina, but this barrier is often degraded in people with retinal diseases.
  • And which patients do you target for the treatment—those in the early or late stage of their disease? For each therapy, there will be different windows of treatment opportunity.

These issues constitute just the tip of the proverbial iceberg; there’s so much more to consider, including clinical-trial design, therapy manufacturing and regulatory compliance.

Before the start of the 2016 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), the Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) and Casey Eye Institute at Oregon Health & Science University hosted “Innovation Summit: Retinal Cell and Gene Therapy.” It convened many of the world’s best retinal surgeons and stem-cell and gene-therapy developers to share their insights and lessons learned in taking on these important questions and challenges.

While there were seven outstanding stem-cell presentations during the summit, I want to highlight two that were particularly intriguing.

Jeffrey Stern, M.D., Ph.D., co-founder of the Neural Stem Cell Institute (NSCI), discussed how the human retina has its own resident stem cells, which his group is working to harness as a therapy for diseases like AMD. In AMD, the disease causes degeneration of supportive cells known as retinal pigment epithelium, or RPE. When RPE are lost, the photoreceptors, the cells that make vision possible, die off as well, and central vision is lost.

Along with his wife and NSCI co-founder, Sally Temple, Ph.D., Stern is leading an effort to coax dormant stem cells in the patient’s retina to become new RPE. While it isn’t as far along as other RPE-replacement therapies, some of which are in early clinical trials, the NSCI “grow your own” approach would avoid many of the issues—including immune-system reactions, manufacturing and transplantation—associated with other stem-cell therapies.

I’d also like to applaud the opening stem-cell presentation delivered by consultant Jane Lebkowski, Ph.D. She has been involved with the California Project to Cure Blindness, which launched a clinical trial of an RPE-replacement therapy derived from blastocysts. She gave a nice summary of the many considerations one must make in launching a human stem-cell study. I have no doubt that the many summit attendees working toward clinical trials found her discussion to be invaluable. There’s nothing like experiential knowledge from someone who has successfully met the challenge you are trying to conquer.

The two-day summit included 25 presentations and 150 attendees. It was the third ARVO-associated summit hosted by FFB-CRI and Casey.