Public Release: 

First study using human embryonic stem cells for macular degeneration shows they are safe and lead to some vision improvement

Lancet

The Lancet today reports the use of human embryonic stem cells to treat macular degeneration in human beings. It is the first report of the use of such cells in humans for any purpose. The study involved one elderly patient and one young patient with different forms of macular degeneration that had led to severe vision loss. The transplants appeared safe after four months, and both patients had some improvement in vision. The future therapeutic goal will be to treat patients earlier in the disease process, in order to boost the prospects of improving or retaining sight in new patients. The study is by Dr Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, Marlborough, MA, USA, and Professor Steven Schwartz, Jules Stein Eye Institute Retina Division at the University of California, Los Angeles, CA, USA, and their colleagues.

Use of hESC is controversial for a number of reasons. There is an ongoing ethical debate surrounding whether or not embryonic stem cells should be used in treatments (on the basis that an embryo can be regarded as the earliest form of human life). There are also biological risks of use, including teratoma formation (a type of cancer that occurs when stem cells differentiate into multiple cell types and form incompatible tissues that can include teeth and hair).

Cell reprogramming technologies are in development that will hopefully lead to rejection becoming a thing of the past. However, until then, so-called 'immunoprivileged' sites (that do not produce a strong immune response) such as the eye, will likely be the first parts of the human body to benefit from hESC transplants. It is the existence of the blood-ocular barrier in the eye that limits the immune response within the eye.

This study assessed transplantation of hESC-derived retinal pigment epithelium (RPE) into the subretinal space (under the retina of the eye) of one eye in two patients. One patient (female, in her 70s) had dry age-related macular degeneration (the leading cause of blindness in the developed world), and the other (female, in her 50s) had Stargardt's macular dystrophy, the most common form of macular degeneration in young patients. 50,000 RPE cells were injected through a fine cannula into the subretinal space of each patient's eye.

Patients received low-dose immunosuppression therapy, which doctors began to taper off after 6-weeks. After surgery, structural evidence confirmed cells had attached to Bruch's membrane and survived throughout the study period. No safety concerns emerged in the four months post-transplant: no teratoma or other hyperproliferation were detected, and there were no signs of rejection or abnormal cell growth.

The authors say that in patients who began with poor vision (both patients were legally blind), it is difficult to ascertain definite improvements in vision unless such improvements are spectacular. While neither patient lost vision, some standard tests suggested vision had improved in both. The patient with Stargardt's disease went from being able to only see hand movements at first, to being able to see single finger movements, through to 20/800 vision. Using the

Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, the patient went from being unable to read any letters to being able to read five letters. In the patient with dry age-related macular degeneration, the improvement was from being able to read 21 letters on this chart pre-treatment up to a peak of 33 after 2 weeks, before settling at a stable reading level of 28 letters.

The authors conclude: "Our study is designed to test the safety and tolerability of hESC-RPE in patients with advanced-stage Stargardt's macular dystrophy and dry age-related macular degeneration. So far, the cells seem to have transplanted into both patients without abnormal proliferation, teratoma formation, graft rejection, or other untoward pathological reactions or safety signals. Continued follow-up and further study is needed. The ultimate therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue."

Dr Lanza adds*: "It has been over a decade since the discovery of human embryonic stem cells. This is the first report of hESC-derived cells ever transplanted into patients, and the safety and engraftment data to-date looks very encouraging. Although several new drugs are available for the treatment of the wet type of AMD, no proven treatments currently exist for either dry-AMD or Stargardt's disease. Despite the progressive nature of these conditions, the vision of both patients appears to have improved after transplantation of the cells, even at the lowest dosage. This is particularly important, since the ultimate goal of this therapy will be to treat patients earlier in the course of the disease where more significant results might potentially be expected."

In a linked Comment, Professor Anthony Atala, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, NC, USA, "The potential to use human embryonic derived cells with a therapeutic effect in patients is now finally realised... The ultimate therapeutic goal for patients with visual loss would be to treat them earlier in the disease processes, hopefully increasing the likelihood of visual rescue. Much remains to be seen- literally.

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Dr Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, Marlborough, MA, USA, please contact via either Tony Russo or Martina Schwarzkopf at Russo Partners. Martina Schwarzkopf T) +1 212-845-4292 / +1 347-591-8785 E) martina.schwarzkopf@russopartnersllc.com

Tony Russo T) +1 212-845-4251 E) tony.russo@russopartnersllc.com

For Dr. Steven D. Schwartz, Ahmanson Professor of Ophthalmology, Chief, Retina Division, Jules Stein Eye Institute, Los Angeles, CA, USA, please contact Elaine Schmidt, Media Relations T) 310-794-2272 E) Schwartz@jsei.ucla.edu

For Professor Anthony Atala, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, NC, USA, please contact the Press Office. T) +1 336-716-4453 / +1 336-716-4587 E) aatala@wakehealth.edu

Notes to editors: *quote direct from Dr Lanza, not within Article
**for video footage, please see contact for Dr Lanza above

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