Effect of gene therapy on visual function in Leber's congenital amaurosis.
James W B Bainbridge,Alexander J. Smith,Susie S Barker,Scott J Robbie,Robert H. Henderson,Kamaljit S. Balaggan,Ananth C. Viswanathan,Graham E. Holder,Andrew Stockman,Nick Tyler,Simon M. Petersen-Jones,Shomi S. Bhattacharya,Adrian J. Thrasher,Fred W. Fitzke,Barrie J Carter,Gary S. Rubin,Anthony T. Moore,Robin R. Ali +17 more
TL;DR: Three young adult patients with early-onset, severe retinal dystrophy were administered subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human R PE65 promoter.
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Abstract: Early-onset, severe retinal dystrophy caused by mutations in the gene encoding reti- nal pigment epithelium-specific 65-kDa protein (RPE65) is associated with poor vi- sion at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Gold- mann perimetry in any of the three patients. We detected no change in retinal re- sponses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)
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Citations
Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
Lourdes Valdés-Sánchez,Sara Borrego-González,Adoración Montero-Sánchez,Simone Massalini,B. de la Cerda,Aránzazu Díaz-Cuenca,Francisco J. Diaz-Corrales +6 more
TL;DR: N-MSiNPs are safe for retinal delivery and thus a potential alternative to viral vectors and were able to deliver a therapeutic transgene candidate for RP, PRPF31, both in vitro and in vivo.
Blindness in neurological disease: a short overview of new therapies from translational research.
TL;DR: The 16-year-old school girl remained with no perception of light vision in both eyes and dense bilateral optic atrophy, and was otherwise completely well on recovery.
13
Clinical Protocols for the Evaluation of Rod Function.
Krunoslav Stingl,Katarina Stingl,Katarzyna Nowomiejska,Laura Kuehlewein,Susanne Kohl,Melanie Kempf,Torsten Strasser,Ronja Jung,Barbara Wilhelm,Tobias Peters,Carina Kelbsch,Karl Ulrich Bartz-Schmidt,Hana Langrová,Eberhart Zrenner +13 more
TL;DR: In comparison to DAC perimetry, CPC shows a superior intervisit repeatability in detecting functional changes in the rod population in an objective way with lower spatial resolution.
13
Phoenix rising: gene therapy makes a comeback.
TL;DR: In this review, various gene therapy vectors progressing into clinical development and pivotal advances in gene therapy trials will be discussed.
Shared Decision-Making, Control Preferences and Psychological Well-Being in Patients with RPE65 Deficiency Awaiting Experimental Gene Therapy
TL;DR: Important data is generated about the psychological situation of patients awaiting potential enrollment in clinical trials, which can be used to improve patient care in the increasing number of future gene therapy trials around the world.
13
References
Gene therapy restores vision in a canine model of childhood blindness.
Gregory M. Acland,Gustavo D. Aguirre,Jharna Ray,Qi Zhang,Tomas S. Aleman,Artur V. Cideciyan,Susan E. Pearce-Kelling,Vibha Anand,Yong Zeng,Albert M. Maguire,Samuel G. Jacobson,William W. Hauswirth,Jean Bennett +12 more
TL;DR: The results indicate that visual function was restored in this large animal model of childhood blindness, and gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported.
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Rpe65 is necessary for production of 11- cis-vitamin A in the retinal visual cycle
T. Michael Redmond,Shirley Yu,Eric Lee,Dean Bok,D. I. Hamasaki,Ning Chen,Patrice Goletz,Jian Xing Ma,Rosalie K. Crouch,Karl Pfeifer +9 more
TL;DR: Disruption of the RPE-based metabolism of all-trans-retinyl esters to 11-cis-retinal thus appears to underlie the Rpe65-/- phenotype, although cone pigment regeneration may be dependent on a separate pathway.
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Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.
Sumin Gu,Debra A. Thompson,C. R.Srisailapathy Srikumari,Birgit Lorenz,Ulrich Finckh,Aileen Nicoletti,K. R. Murthy,Michaela Rathmann,Govindasamy Kumaramanickavel,Michael J. Denton,Andreas Gal +10 more
TL;DR: The analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation, two point mutations affecting splicing and two small re-arrangements on a total of nine alleles of five patients with arCSRD.
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RPE65 is the isomerohydrolase in the retinoid visual cycle
TL;DR: It is demonstrated that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle.
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