期刊
PLOS ONE
卷 10, 期 12, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0143846
关键词
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资金
- QLT Inc. [QLT091001]
- Wynn-Gund Translational Research Acceleration Program Enhanced Research and Clinical Training Award, National Neurovision Research Institute (NNRI) - Foundation Fighting Blindness (FFB) [NNCD-CL-0310.0049-JHU-WG]
- Macular Degeneration Research Award, American Health Assistance Foundation/BrightFocus Foundation (AHAF) [M2010042]
- Research to Prevent Blindness
- Baylor-Johns Hopkins Center for Mendelian Genetics (National Human Genome Research Institute, NHGRI/NIH) [1U54HG006542-01]
- Canadian Foundation Fighting Blindness
- Canadian Institutes for Health Research
- Fonds de la Recherche en Santee du Quebec
- Reseau Vision
- NIH
- National Institute for Health Research UK (Moorfields Biomedical Research Centre)
- National Institute for Health Research [NF-SI-0507-10204] Funding Source: researchfish
Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m(2)/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a >= 20% increase and 4 of 18 (22%) showed a >= 40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a >= 5 and >= 10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 +/- 4.8 mu m, mean +/- 95% CI) than non-responders (3.5 +/- 1.2 mu m). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.
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