Tags

Type your tag names separated by a space and hit enter

Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives.
Prog Retin Eye Res. 2019 Dec 30 [Online ahead of print]PR

Abstract

Due to improved phenotyping and genetic characterization, the field of 'incurable' and 'blinding' inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial.

Authors+Show Affiliations

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: jacobsos@pennmedicine.upenn.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31899291

Citation

Garafalo, Alexandra V., et al. "Progress in Treating Inherited Retinal Diseases: Early Subretinal Gene Therapy Clinical Trials and Candidates for Future Initiatives." Progress in Retinal and Eye Research, 2019, p. 100827.
Garafalo AV, Cideciyan AV, Héon E, et al. Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives. Prog Retin Eye Res. 2019.
Garafalo, A. V., Cideciyan, A. V., Héon, E., Sheplock, R., Pearson, A., WeiYang Yu, C., Sumaroka, A., Aguirre, G. D., & Jacobson, S. G. (2019). Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives. Progress in Retinal and Eye Research, 100827. https://doi.org/10.1016/j.preteyeres.2019.100827
Garafalo AV, et al. Progress in Treating Inherited Retinal Diseases: Early Subretinal Gene Therapy Clinical Trials and Candidates for Future Initiatives. Prog Retin Eye Res. 2019 Dec 30;100827. PubMed PMID: 31899291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives. AU - Garafalo,Alexandra V, AU - Cideciyan,Artur V, AU - Héon,Elise, AU - Sheplock,Rebecca, AU - Pearson,Alexander, AU - WeiYang Yu,Caberry, AU - Sumaroka,Alexander, AU - Aguirre,Gustavo D, AU - Jacobson,Samuel G, Y1 - 2019/12/30/ PY - 2019/10/27/received PY - 2019/12/21/revised PY - 2019/12/26/accepted PY - 2020/1/4/pubmed PY - 2020/1/4/medline PY - 2020/1/4/entrez KW - ABCA4 KW - BCM KW - CNGA3 KW - CNGB3 KW - Gene therapy KW - Genetic retinal degenerations KW - Leber congenital amaurosis KW - MERTK KW - MYO7A KW - Molecular mechanisms KW - NPHP5 KW - OPN1LW KW - OPN1MW KW - PDE6B KW - REP1 KW - RLBP1 KW - RPE65 KW - RPGR KW - RPGRIP1 KW - Retinitis pigmentosa KW - TULP1 SP - 100827 EP - 100827 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Due to improved phenotyping and genetic characterization, the field of 'incurable' and 'blinding' inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/31899291/Progress_in_treating_inherited_retinal_diseases:_Early_subretinal_gene_therapy_clinical_trials_and_candidates_for_future_initiatives L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(19)30114-4 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.