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Researcher ‘cautiously optimistic’ about future of regenerative medicine to treat AMD
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Regenerative medicine has opened a new frontier in macular degeneration. Important steps have been made, and there are reasons to be optimistic about the future.
“Cautiously optimistic,” Demetrios G. Vavvas, MD, PhD, told Ocular Surgery News. “This path holds enormous promise, but the way is still long and we should avoid jumping to conclusions.”
With Michael J. Young, PhD, Vavvas is co-director of the Ocular Regenerative Medicine Institute of Massachusetts Eye and Ear, and part of a research group that has made significant advances in the understanding of stem cell transplantation, tissue engineering and nanoparticles for drug delivery.
“Specifically for macular degeneration, there is quite a lot happening, and some of the studies have reached the stage of clinical trials. We are involved in some of these trials with our patients and surgeons,” Vavvas said.
Current phase 1 and phase 2 trials are evaluating the safety of retinal pigment epithelium (RPE) cell transplantation, the support cells of photoreceptors. The RPE is a major insult site in macular degeneration, subject to death and malfunction, Vavvas explained.
“One of the ideas is to replenish diseased RPE cells by transplanting healthy cells, which are derived from stem cells,” he said.
He said that, contrary to what is commonly thought, what is used in clinical trials are induced pluripotent stem (iPS) cells or other stem cell types, “instructed” to develop RPE cells.
“What we read in the media is that we are transplanting stem cells, which is incorrect. What we transplant are differentiated cells, namely RPE cells derived most often from induced iPS cells. Not bona fide stem cells, but cells that were derived from stem cells,” he said.
Two main approaches are used in patients with AMD. One approach is to transplant free-floating cells (cell suspensions) and let them sit in the subretinal space. The other is to grow cells on a scaffold and deliver a monolayer sheet of cells to the transplant site in the subretinal space.
“These are the ideas that are currently tested in clinical trials, but another piece of misinformation I would like to dispel is that nothing has so far been tested for efficacy. Trials are currently evaluating safety. Reports on efficacy are inaccurate and grossly exaggerating. My blunt assessment is that right now none of these methods has been proved to help humans. We are progressing, but the current technology is probably still immature and we do not expect efficacy just yet,” Vavvas said.
Other approaches
Other groups are attempting to implant the photoreceptor cells or to transplant the RPE, the photoreceptors and the choroidal endothelium. This research is at an even earlier stage.
Encapsulated cell therapy-based approaches for sustained secretion of ciliary neurotrophic factor to the vitreous were also attempted, but trials did not meet efficacy endpoints and were therefore discontinued. Other research groups are exploring the potential of bone marrow-derived hematopoietic stem cells administered intravitreally.
At Mass Eye and Ear, a group of researchers led by the work of M. Young has explored the potential of photoreceptor replacement therapy in the juvenile form of retina degeneration, which has now moved on to clinical trials.
“Another approach that we attempted and published 2 years ago was to regress certain AMD features by administering high-dose statins, namely atorvastatin 80 mg once a day for 1 year. The same drug has shown regression of atherosclerotic plaques in cardiovascular disease, and our aim was to see if a similar effect could be obtained on drusen deposits in AMD,” Vavvas said.
In 10 of the 23 patients enrolled in the study, the treatment resulted in regression of drusenoid pigment epithelial detachments and a small visual gain of 3.3 letters.
“This was a very specific population of AMD patients, but it might still be a way worth pursuing in larger studies,” Vavvas said.
In the lab, Mass Eye and Ear is now setting a new course, combining regeneration biology approaches and neuroprotection approaches for incrementally better results.
“So far, these two approaches have been investigated separately. Some people are studying cell death and how to slow down cell death, and other people are studying how to regenerate cells. In cell biology, we have learned quite a lot on how to slow down cell death. What we are trying to do right now is to apply these results in animal models of regenerative approaches of transplantation of cells to increase the efficacy of the regeneration and transplantation of precursor cells. We have preliminary data that look encouraging,” Vavvas said.
Overhyping does not help
“We are in an exciting era, a lot is ongoing, and eventually the breakthrough time will come. But we should be clear that we are still at the start of a very long path. None of the current strategies is yet going to be the answer. They are good steps along the way, have had large resonance, but they are very costly and, most importantly, have not overcome many of the hurdles,” Vavvas said.
What he says to his patients who want to be part of current trials is “do not think you are going to be immediately helped. You are going to help science, but it is unlikely you are going to see better.”
Patients nevertheless participate because they want to help science, doctors who are investing efforts in this research and future generations. Their generous contribution should deserve attention in the news, Vavvas said.
“Fighting against macular degeneration is a huge challenge. A lot is still unknown about the disease, and we must proceed with caution without jumping to conclusion,” he said. “Overhyping does not help anyone; it only creates false hopes.” – by Michela Cimberle
- For more information:
- Demetrios G. Vavvas, MD, PhD, can be reached at Massachusetts Eye and Ear, 243 Charles St., Boston, MA 02114; email: vavvas@meei.harvard.edu or demetrios.vavvas@gmail.com.
Disclosure: Vavvas reports no relevant financial disclosures.