Cell therapy advances for retinal disease

February 1, 2011

In the first in-human study fo human umbilical tissue-derived cells as cell-based therapy for retinal degenerative diseases, all seven patients tolerated the subretinal injection well and had no postoperative visual loss.

In the first in-human study of human umbilical tissue-derived cells as cell-based therapy for retinal degenerative diseases, all seven patients tolerated the subretinal injection well and had no postoperative visual loss.

One patient had increased light sensitivity and showed a demonstrable and repeatable improvement in full-field stimulus thresholds, changes that would be difficult to explain by a learning experience or random change, according to Peter J. Francis, MD, PhD, associate professor and director, Translational Clinical Trials Center, Casey Eye Institute, Oregon Health & Science University, Portland.

"One out of seven isn't very much, but if you're looking for any possible signal, that might be it," said Dr. Francis, whose lab was the lead institution in the study. "Otherwise, patients didn't lose vision.

All of the participants had advanced retinitis pigmentosa (RP), no better than hand-motion vision. They were enrolled from three institutions in the United States and underwent vitrectomy and single unilateral extramacular subretinal injection of an allogenic cellular product known as CNTO2476.

The cells were produced by the Stem Cell Organization, which is part of the J&J Biotechnology Center of Excellence, Centocor R&D Inc., which is now planning to move forward with studies of additional indications and additional trials.

Dr. Francis reported the latest findings at the 2010 annual meeting of the Association for Research in Vision and Ophthalmology. In this preliminary study, the three men and four women, with a median age of 62 years, received cell dosages ranging from 47,500 to 470,000 cells delivered transvitreally to the subretinal space through a retinotomy. Follow-up evaluations were conducted for more than 1 year.

Analysis of the results showed no evidence of immune rejection. Two patients developed post-surgical retinal detachments, which may have been related to non-closure of the retinotomy site.

Although the participants in a phase I study are typically normal, healthy individuals, the nature of this therapy, which required a vitrectomy, necessitated choosing subjects with a retinal degenerative condition, Dr. Francis said.

"We thought that the chances of seeing efficacy were very limited, but because this was the first in-human use of cells in this manner, and certainly in the eye, we thought that they would be the target group," he said. "If we were going to see efficacy, it would be in one of these retinal degenerations like RP and possibly age-related macular degeneration (AMD)."

Although it was encouraging that there was no evidence of an immune rejection, the broader implication of the phase I study for the field of stem cell research was that these cells could be successfully implanted in the retina without a deleterious effect or immune response, Dr. Francis said.

"This was the first and tentative, careful step into transplantation and use of stem cells for retinal disease, and the results were encouraging," he added. "It was a small, careful, and carefully planned step forward for the field."

Additional clinical trials

Plans for additional clinical trials of CNTO2476 are proceeding, according to Paul Williamson, MD, senior director, the Stem Cell Organization of the J&J Biotechnology Center of Excellence, Centocor R&D Inc., Radnor, PA.

"We have an interest in developing this product in retinal degeneration, and we have plans to move forward with a later-stage trial to see if there is proof of concept," he said.

A phase I/IIa study of the safety and efficacy of CNTO2476 in patients with AMD was posted on http://www.clinicaltrials.gov/ in October. At that time, the trial was not open for patient recruitment. According to the Web site, the first phase of the trial will be a dose escalation study, and the second portion will enroll additional patients randomly assigned to one of the two doses selected from the first portion.

FYI

Peter J. Francis, MD, PhD
Phone: 503/418-1627
E-mail: francisp@ohsu.edu

Dr. Francis has a consulting relationship with the Stem Cell Organization of the J&J Biotechnology Center of Excellence, Centocor R&D Inc., Radnor, PA.

Paul Williamson, MD
E-mail: PWillia5@its.jnj.com

Dr. Williamson is an employee of the Stem Cell Organization of the J&J Biotechnology Center of Excellence, Centocor R&D Inc., Radnor, PA.