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Gene Therapy for Retinitis Pigmentosa Caused by MFRP Mutations: Human Phenotype and Preliminary Proof of Concept
- Publication Year :
- 2011
- Publisher :
- Mary Ann Liebert, Inc., 2011.
-
Abstract
- Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy.
- Subjects :
- Retinal degeneration
Pathology
medicine.medical_specialty
Gene therapy of the human retina
Retinal pigment epithelium
medicine.diagnostic_test
Retinal
Gene delivery
Apical membrane
Biology
medicine.disease
Molecular biology
chemistry.chemical_compound
medicine.anatomical_structure
chemistry
Retinitis pigmentosa
Genetics
medicine
Molecular Medicine
Molecular Biology
Research Articles
Electroretinography
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....acef9ab2cff06058ac72cc75b219f0e5