التفاصيل البيبلوغرافية
| العنوان: |
Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial |
| المؤلفون: |
Jean Bennett, Jessica I. W. Morgan, Carmela Acerra, Kathleen A. Marshall, Katherine A. High, Daniel C. Chung, Xiaosong Zhu, Alberto Auricchio, Enrico Maria Surace, Bernd Hauck, Frauke Coppieters, Gui-Shuang Ying, Albert M. Maguire, Kenneth S. Shindler, Sandro Banfi, Jenni Fer Uvellman Mcdonnell, Nicholas J. Volpe, Arkady Lyubarsky, Ann Fulton, Leslie Raffini, Eric A. Pierce, Elfride De Baere, Olga Zelenaia, Jeannette L. Bennicelli, J. Fraser Wright, Francesco Testa, T. Michael Redmond, Junwei Sun, Edwin M. Stone, Federico Mingozzi, Francesca Simonelli, Bart P. Leroy, Settimio Rossi |
| المساهمون: |
Maguire, Am, High, Ka, Auricchio, A, Wright, Jf, Pierce, Ea, Testa, Francesco, Mingozzi, F, Bennicelli, Jl, Ying, G, Rossi, Settimio, Fulton, A, Marshall, Ka, Banfi, Sandro, Chung, Dc, Morgan, Ji, Hauck, B, Zelenaia, O, Zhu, X, Raffini, L, Coppieters, F, De Baere, E, Shindler, K, Volpe, Nj, Surace, Em, Acerra, C, Lyubarsky, A, Redmond, Tm, Stone, E, Sun, J, Mcdonnell, Jw, Leroy, Bp, Simonelli, Francesca, Bennett, J., Auricchio, Alberto, Testa, F, Rossi, S, Banfi, S, Surace, Enrico Maria, Simonelli, F |
| المصدر: |
Lancet (London, England). 374(9701) |
| سنة النشر: |
2009 |
| مصطلحات موضوعية: |
Retinal degeneration, Male, Visual acuity, genetic structures, Visual Acuity, Blindness, chemistry.chemical_compound, Mice, Medicine, Child, media_common, Age Factors, General Medicine, Dependovirus, gene therapy, Leber’s congenital amaurosi, Treatment Outcome, Disease Progression, Leber's congenital amaurosis, Female, medicine.symptom, Safety, Retinopathy, Adult, cis-trans-Isomerases, medicine.medical_specialty, Adolescent, Genetic Vectors, Dark Adaptation, Optic Atrophy, Hereditary, Leber, Article, Injections, Young Adult, Nystagmus, Physiologic, Ophthalmology, Electroretinography, media_common.cataloged_instance, Animals, Humans, European union, Eye Proteins, Dose-Response Relationship, Drug, business.industry, Infant, Newborn, Retinal, Genetic Therapy, medicine.disease, eye diseases, Disease Models, Animal, RPE65 gene, RPE65, chemistry, Cis-trans-Isomerases, Mutation, business, Carrier Proteins |
| الوصف: |
Background Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis.Methods We assessed the retinal and visual function in 12 patients (aged 8-44 years) with RPE65-associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1.5x10(10) vector genomes), medium (4.8x10(10) vector genomes), or high dose (1.5x10(11) vector genomes) for up to 2 years.Findings AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The study is registered with ClinicalTrials.gov, number NCT00516477.Interpretation The safety, extent, and stability of improvement in vision in all patients support the use of AAV mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain. Background: Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis. Methods: We assessed the retinal and visual function in 12 patients (aged 8-44 years) with RPE65-associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1·5×1010 vector genomes), medium (4·8×1010 vector genomes), or high dose (1·5×1011 vector genomes) for up to 2 years. Findings: AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The study is registered with ClinicalTrials.gov, number NCT00516477. Interpretation: The safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain. Funding: Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia, Foundation Fighting Blindness, Telethon, Research to Prevent Blindness, F M Kirby Foundation, Mackall Foundation Trust, Regione Campania Convenzione, European Union, Associazione Italiana Amaurosi Congenita di Leber, Fund for Scientific Research, Fund for Research in Ophthalmology, and National Center for Research Resources. © 2009 Elsevier Ltd. All rights reserved. |
| تدمد: |
1474-547X |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83e3ef7f273825996ee1f6bcdf200da5Test
https://pubmed.ncbi.nlm.nih.gov/19854500Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....83e3ef7f273825996ee1f6bcdf200da5 |
| قاعدة البيانات: |
OpenAIRE |
