Date of this Version
Expert Opinion on Orphan Drugs
10.1517/21678707.2015.1030393 PMCID: PMC4487613
Introduction: Inherited retinal degenerations (IRDs) have long been considered untreatable and incurable. Recently, one form of early-onset autosomal recessive IRD, Leber congenital amaurosis (LCA) caused by mutations in RPE65 (retinal pigment epithelium-specific protein 65 kDa) gene, has responded with some improvement of vision to gene augmentation therapy and oral retinoid administration. This early success now requires refinement of such therapeutics to fully realize the impact of these major scientific and clinical advances.
Areas covered: Progress toward human therapy for RPE65-LCA is detailed from the understanding of molecular mechanisms to preclinical proof-of-concept research to clinical trials. Unexpected positive and complicating results in the patients receiving treatment are explained. Logical next steps to advance the clinical value of the therapeutics are suggested.
Expert opinion: The first molecularly based early-phase therapies for an IRD are remarkably successful in that vision has improved and adverse events are mainly associated with surgical delivery to the subretinal space. Yet, there are features of the gene augmentation therapeutic response, such as slowed kinetics of night vision, lack of foveal cone function improvement and relentlessly progressive retinal degeneration despite therapy, that still require research attention.
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gene therapy, Leber congenital amaurosis, photoreceptors, retina, retinal pigment epithelium, retinoid cycle
Jacobson, S. G., Cideciyan, A. V., Aguirre, G. D., Roman, A. J., Sumaroka, A., Hauswirth, W. W., & Palczewski, K. (2015). Improvement in Vision: A New Goal for Treatment of Hereditary Retinal Degenerations. Expert Opinion on Orphan Drugs, 3 (5), 563-575. http://dx.doi.org/10.1517/21678707.2015.1030393 PMCID: PMC4487613
Date Posted:19 April 2018
This document has been peer reviewed.