An Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) system—developed by researchers at the University of California, San Francisco, and University of California, Berkeley—has proven an intraocular implant able to preserve photoreceptors in patients with retinitis pigmentosa (RP), a condition that causes blindness. The implant, called NT-501 and developed by Neurotech Pharmaceuticals, Inc. (Lincoln, RI), consists of human cells genetically modified to secrete ciliary neurotrophic factor (CNTF)—a nerve growth factor capable of rescuing and protecting dying photoreceptors.
Neurotech calls the AOSLO “a breakthrough diagnostic technology” because it overcomes a major obstacle in the study of retinal degeneration: It is able to noninvasively measure cone photoreceptor cells—those cells of the retina responsible for fine central and color vision--and quantitatively measure their rate of degeneration in the eyes of living subjects. “These results suggest that AOSLO may play a meaningful role in the early assessment of photoreceptor loss due to retinitis pigmentosa well before serious functional loss is detected by standard measures of visual function, and that NT-501 may play an important neuroprotective role,” said Paul Sieving, MD, PhD, Director of the National Eye Institute and Principal Investigator of Neurotech’s Phase 1 study of NT-501 in RP.
Results of the study are reported in the journal Investigative Ophthalmology & Visual Science (April 2011, Vol. 52). The study was led by Jacque Duncan, MD, Professor of Clinical Ophthalmology, University of California, San Francisco, and Austin Roorda, PhD, Professor of Optometry and Vision Science, Chair and Head Graduate Advisor in the Vision Science Program, University of California, Berkeley. “We are extremely encouraged by the photoreceptor preserving effect of NT-501 seen in this study as well as the usefulness of AOSLO as a diagnostic tool for retinitis pigmentosa progression. Larger studies using AOSLO are urgently needed to confirm the photoreceptor protective effect of NT-501 treatment in patients with retinal degeneration,” said Duncan.
“These exciting results add to the growing body of evidence that NT-501 will benefit individuals who suffer from retinitis pigmentosa and other retinal degenerative diseases,” stated Ted Danse, Chief Executive Officer of Neurotech. “Given the slow progression of these diseases, measuring improvements in visual function appears to require extremely lengthy trials. We believe tools such as AOSLO that measure photoceptor preservation can play an important role in defining meaningful and measurable near-term benefits of treatment of such slow-progressing, debilitating diseases,” added Danse.
In the prospective study, two patients with RP and one patient with Usher syndrome type 2, a rare genetic disorder characterized by vision loss due to RP and bilateral hearing loss, were evaluated by AOSLO at baseline and at 3, 6, 12, 18 and 24 months following implantation. Patients studied were selected from Neurotech’s Phase 2 NT-501 study in patients with early-stage RP. For each patient, one eye received an NT-501 implant while the fellow eye received sham-treatment. AOSLO quantitatively assessed photoreceptor loss by measuring cone density and average cone spacing at several prospectively identified locations in the retina of each patient, aggregating repeated measures for all data points, and comparing results for the active- and sham-treated eyes. No increase in cone spacing or decrease in cone density was observed in any of the eyes treated with NT-501. An increase in cone spacing and a decrease in cone density are both indicative of photoreceptor loss. In addition, the results demonstrated a statistically significant preservation of cone photoreceptors in the eyes of all three subjects treated with the NT-501 implant versus sham-treated eyes. Cone spacing increased by 2.9% more per year in sham-treated eyes than in NT-501-treated eyes (p = 0.001), and cone density decreased by 9.1% more per year in sham-treated eyes than in NT-501-treated eyes (p = 0.002).
Standard scanning laser ophthalmoscopy (SLO) uses confocal imaging to obtain high-resolution optical images at varying depths within the eye. The use of adaptive optics (AO) improves SLO by removing aberrations in retinal images caused by imperfections in the eye’s optics. The improved image makes it possible to see individual cone photoreceptor cells.
Neurotech's proprietary Encapsulated Cell Therapy (ECT) platform enables bypass of the blood-retinal barrier, which overcomes a major obstacle in the long-term treatment of retinal disease. NT-501 has received orphan and fast-track designations for the treatment of visual loss in RP from the United States Food and Drug Administration (FDA).
Posted by Lee Mather
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