+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype and preliminary proof of concept



Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype and preliminary proof of concept



Human Gene Therapy 23(4): 367-376



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053367085

Download citation: RISBibTeXText

PMID: 22142163

DOI: 10.1089/hum.2011.169


Related references

A new autosomal recessive syndrome consisting of posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disc drusen is caused by a MFRP gene mutation. Molecular Vision 12: 1483-1489, 2006

Mutations in TULP1, NR2E3, and MFRP genes in Indian families with autosomal recessive retinitis pigmentosa. Molecular Vision 18(): 1165-1174, 2012

Retinal laminar architecture in human retinitis pigmentosa caused by Rhodopsin gene mutations. Investigative Ophthalmology & Visual Science 49(4): 1580-1590, 2008

RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations. Frontiers in Molecular Neuroscience 7: 25-25, 2014

Phenotype characterization in two families with X-linked Retinitis Pigmentosa caused by RPGR mutations. IOVS 41(4): S192, March 15, 2000

Two novel mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in X-linked retinitis pigmentosa (RP3). Mutations in brief no. 172. Online. Human Mutation 12(3): 212-213, 2000

A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family. Molecular Vision 16(): 1620-1628, 2010

Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a family with the nanophthalmos-retinitis pigmentosa complex. Molecular Vision 15(): 1794-1798, 2009

Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes. Molecular Medicine Reports 12(4): 5983-5988, 2016

Two novel mutations of the retinitis pigmentosa GTPase regulator gene in two Chinese families with X-linked retinitis pigmentosa. Chinese Medical Journal 115(6): 833-836, 2002

Identification of two mutations of the RHO gene in two Chinese families with retinitis pigmentosa: correlation between genotype and phenotype. Molecular Vision 18(): 3013-3020, 2013

Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene. Investigative Ophthalmology & Visual Science 52(13): 9665-9673, 2012

Slowly progressive retinitis pigmentosa caused by two novel mutations in the MAK gene. Ophthalmic Genetics: 1-4, 2018

Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype. Ophthalmology 117(10): 2026-33, 2033.E1-7, 2010

LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability. Retina (): -, 2016