Phase I Trial Finds Patient-Derived Stem Cell Therapy Safe for Severe Chemical Eye Burns

A biopsy small enough to leave the donor eye intact, a graft grown over two to three weeks in a lab across town, and then a transplant into the burned eye: that is the sequence at the center of a phase I trial published August 18 in Science Advances. Researchers led by Mass Eye and Ear, a member of Mass General Brigham, report that the approach, called cultivated autologous limbal epithelial cell transplantation, or CALEC, was safe and well tolerated in the short term in four patients with significant chemical burns to one eye.

The problem it targets is limbal stem cell deficiency. Chemical burns and other eye injuries can cause an irreversible loss of cells in the tissue surrounding the cornea. Patients are left with permanent vision loss, pain and discomfort. Without limbal cells and a healthy eye surface, they cannot receive an artificial cornea transplant, the current standard for vision rehabilitation. Cornea specialists, in the words of principal investigator Dr. Ula Jurkunas, have been hindered by a lack of treatment options with a high safety profile for these patients.

CALEC works by taking stem cells from the patient's healthy eye through a small biopsy. The cells are expanded and grown on a graft at the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber Cancer Institute. After two to three weeks, the graft returns to Mass Eye and Ear and is transplanted into the damaged eye, where it serves as a surface for normal tissue to grow back. Because the cells are the patient's own, the approach is meant to avoid some limitations and risks of existing treatments.

The authors note that autologous stem cell approaches have been described in landmark studies over the past 25 years, and that similar methods are used in Europe. Yet no U.S. research team had developed a manufacturing process and quality control tests that satisfied FDA requirements or showed clinical benefit. Dr. Jerome Ritz, who directs the Dana-Farber facility, said building a process to meet the agency's strict tissue-engineering rules was challenging, and that seeing encouraging outcomes in the first cohort was gratifying. The trial is the first human study of a stem cell therapy funded by the National Eye Institute, part of the NIH.

Five patients with chemical burns to one eye were enrolled and biopsied. Four received CALEC; quality control tests showed the cells from the fifth could not expand adequately. All four treated patients were followed for 12 months.

The first, a 46-year-old man, had his eye surface defect resolve, which made him a candidate for an artificial cornea transplant. The second, a 31-year-old man, had a complete resolution of symptoms, and his vision improved from 20/40 to 20/30. The third, a 36-year-old man, saw his corneal defect resolve and his vision rise from hand motion, meaning he could only perceive broad movements like waving, to 20/30. The fourth, a 52-year-old man, initially had a biopsy that did not yield a viable graft. He tried again three years later, received a successful transplant, and improved from hand motion to counting fingers before getting an artificial cornea. In all, two patients went on to corneal transplants and two reported significant vision improvement without further treatment.

The study was designed to assess preliminary safety and feasibility, not to prove effectiveness, and four patients is a very small sample. The team is finalizing the next phase, which will follow 15 CALEC patients for 18 months to better judge efficacy. The work involved Boston Children's Hospital, led by Dr. Myriam Armant, and the Jaeb Center for Health Research, with funding from NEI/NIH grants. The procedure is patent pending, and Jurkunas and Dr. Reza Dana disclose equity in Ocucell, a company interested in developing cell-based eye therapies.