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

Astra Dinculescu, Jackie Estreicher, Juan C. Zenteno, Tomas S. Aleman, Sharon B. Schwartz, Wei Chieh Huang, Alejandro J. Roman, Alexander Sumaroka, Qiuhong Li, Wen-Tao Deng, Seok-Hong Min, Vince A. Chiodo, Andy Neeley, Xuan Liu, Xinhua Shu, Margarita Matias-Florentino, Beatriz Buentello-Volante, Sanford L. Boye, Artur V. Cideciyan, William W. HauswirthSamuel G. Jacobson

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


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 ß-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.
Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalHuman Gene Therapy
Issue number4
Early online date26 Jan 2012
Publication statusPublished - Apr 2012


  • MFRP mutations
  • RP
  • gene-based therapy
  • retinal degeneration


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