Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT)
| Autor: | Gislin Dagnelie, Anthony T. Moore, Claire S Barnes, L. Ingeborgh van den Born, Simona Degli Eposti, Hendrik P. N. Scholl, Ronald A. Schuchard, Ava K Bittner, David A. Saperstein, Robert K. Koenekoop, Wadih M. Zein, Yuquan Wen, Gerald A. Fishman, David G. Birch, Ditta Zobor, Kristen Bowles, Eberhart Zrenner, Janine D. Mendola, Emily Fletcher, Michel Michaelides, Frederick T Collison |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Retinal degeneration
Male Retinal Ganglion Cells Retinyl Esters Visual acuity Photophobia genetic structures Visual Acuity lcsh:Medicine Administration Oral chemistry.chemical_compound 0302 clinical medicine Drug Dosage Calculations lcsh:Science Child Vitamin A Cerebral Cortex 0303 health sciences Multidisciplinary Middle Aged 3. Good health medicine.anatomical_structure Treatment Outcome Female medicine.symptom Diterpenes Retinitis Pigmentosa Research Article Retinal Neurons Adult cis-trans-Isomerases medicine.medical_specialty Polymorphism Single Nucleotide 03 medical and health sciences Young Adult Ophthalmology Retinitis pigmentosa medicine Anticarcinogenic Agents Humans 030304 developmental biology Retina business.industry lcsh:R Retinal medicine.disease eye diseases Radiography RPE65 chemistry Cis-trans-Isomerases 030221 ophthalmology & optometry lcsh:Q Visual Fields business Acyltransferases |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 12, p e0143846 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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/m2/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 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity. Trial Registration ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01014052","term_id":"NCT01014052"}}NCT01014052 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|