Ciliary neurotrophic factor may be therapeutic for RP

November 8, 2008

Ciliary neurotrophic factor (CNTF), a member of the interleukin family of proteins, seems to be safe and promising for treating patients with retinitis pigmentosa (RP) when delivered into the eye via sequestered live cell intraocular implants, said Paul Sieving, MD, PhD, director of the National Eye Institute, Bethesda, MD.

Ciliary neurotrophic factor (CNTF), a member of the interleukin family of proteins, seems to be safe and promising for treating patients with retinitis pigmentosa (RP) when delivered into the eye via sequestered live cell intraocular implants, said Paul Sieving, MD, PhD, director of the National Eye Institute, Bethesda, MD.

In a phase I non-randomized, open-label clinical trial, CNTF, which has been shown in animal models to rescue photoreceptors from death, was introduced in one eye of 10 patients through a small incision in the sclera in a 6- × 1-mm implant. CNTF is then released into the vitreous. Five patients received low-dose implants and five received higher-dose implants. The capsules remained implanted for 6 months before they were explanted. Preoperatively, three patients had little visual acuity, and seven eyes had measurable visual acuity.

"The outcome of the safety study was good and provided the basis for going forward with other studies; however, more specifically, we found a remarkable change in visual function exceeding 10 letters in three patients," Dr. Sieving said. "These patients with RP with macular atrophy began to recover visual function halfway through the study. There was no change in the untreated fellow eye. The improvement in visual acuity was sustained 6 months after the implants were removed."

He also pointed out that this result led to the idea to use CNTF for geography atrophy in age-related macular degeneration.

The question that must be addressed regarding these patients is how CNTF actually improves visual function. CNTF may be able to rescue dormant-but-not-dead photoreceptors, Dr. Sieving said.

"It is possible that the photoreceptors may remain viable even though they are not functioning," he said, adding that this is a concept that will undergo evaluation in the phase II/III study.