LONDON – The first patient in the first human embryonic stem cell (hESC) trial to be held in Europe left Moorfields Eye Hospital in London on Monday after being treated for macular degeneration. At the same time, Advanced Cell Technology (ACT) Inc., the company behind the trial of the hESC-derived retinal pigment epithelium cells published initial clinical data on the U.S. arm of the study, showing tantalizing early signs of efficacy.

ACT's news is welcome after regenerative medicine pioneer Geron Inc. stopped recruitment for its ground-breaking Phase I acute spinal injury trial last November and abandoned stem cell R&D altogether, blaming the economy not the science. (See BioWorld Today, Nov. 16, 2011.)

ACT's clinical data, due to appear in The Lancet on Thursday, is the first report in a peer-reviewed journal of the use of hESC-derived cells for any purpose.

Both of the patients whose progress is reported in The Lancet have shown an improvement in their vision since being treated with the retinal pigment epithelium cells in July 2011.

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.

Gary Rabin, chairman and CEO of ACT, said the data represented a milestone for the field of regenerative medicine as a whole and "underscore the potential of stem cell therapies to realize the possibility repairing or replacing tissue" damaged by disease.

In total, 50,000 hESC-derived retinal pigment epithelium cells were transplanted into the subretinal space of each patient. The elderly patient, who is in her 70s, has dry age-related macular degeneration, the leading cause of blindness in the developed world, and the other, a woman in her 50s, has Stargardt's macular dystrophy, the most common form of macular degeneration in young patients.

Both patients are classified as legally blind. The patient with Stargardt's disease went from being able to only see hand movements, to being able to see single finger movements, and from being unable to read any letters on a vision chart to being able to read five letters. The patient with dry age-related macular degeneration went from being able to read 21 letters on the chart before treatment, up to a peak of 33 two weeks after treatment, before settling at a stable reading level of 28 letters.

The researchers "have realized the potential to use hESCs therapeutically in human beings," said Anthony Atala, of the Wake Forest Institute for Regenerative Medicine, in Winston-Salem, N.C., in a comment accompanying the paper in The Lancet.

"The results are impressive, especially considering the progressive nature of both diseases," Atala said.

There was structural evidence that the transplanted hESC-derived cells survived and continued to persist. The improvement in vision came along with an apparently clean safety profile, with no sign of tumorgenicity, tissue formation outside the retina or any immune rejection at up to four months post-treatment.

Robert Lanza, CSO of Marlborough, Mass-based ACT, said the safety and engraftment data are very encouraging.

"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," he said. That is important given ACT's aim is to to treat patients earlier in the course of disease, when it might reasonably be expected the results will be better.

Retinal imaging of the patient with Stargardt's showed an increase in pigmentation within the area of the transplant at one week after treatment and throughout the four month follow-up. ACT said that in this patient the cells "appear to engraft in the proper location and assume normal retinal pigment epithelium morphology." However, there was no sign of engraftment and increasing pigmentation in the patient with dry macular degeneration.

Principal investigator Steven Schwartz, of the Jules Stein Eye Institute at the University of California, Los Angeles, said that the positive safety data and the hint of an improvement in vision "makes this is an exciting time for ophthalmology."

Rabin told BioWorld Today in November 2011 that he aimed to raise more money for his hard-up company on the back of positive clinical results. (See BioWorld Today, Nov. 23, 2011.)

The Lancet was bounced into publishing the U.S. clinical trial paper online three days earlier than planned when ACT announced that the first patient had been treated in the UK Phase I/II trial. ACT's share price edged up by 6 percent to 15 cents when the trial data were released.

ACT and Moorfields Eye Hospital received approval for the UK arm of the trial in September 2011. The Phase I/II study will recruit 12 patients in dose-ascending study with three patients per cohort.

The endpoint of the trial is safety at 12 months post-treatment, but James Bainbridge, principal investigator said, "We will have the opportunity to image engraftment of the retinal pigment epithelium noninvasively and to assess any changes in sight."