Development of a Chromatic Pupillography Protocol for the First Gene Therapy Trial in Patients With CNGA3-Linked Achromatopsia
Lisowska L, Lisowski L, Kelbsch C, Maeda F, Richter P, Kohl S, Zobor D, Strasser T, Stingl K, Zrenner E, Peters T, Wilhelm H, Fischer MD, Wilhelm B; for the RD-CURE Consortium (2017)
PURPOSE: To establish a feasible and sensitive pupillographic protocol to assess outer and inner retinal function for the first gene therapy trial in achromatopsia patients (ACHM) with mutations in CNGA3. METHODS: Twenty-seven CNGA3-ACHM patients and 22 age-matched control subjects were tested using chromatic pupillography. Three different protocols were established to assess the pupillary light reflex […]
The Clinical Phenotype of CNGA3-Related Achromatopsia: Pretreatment Characterization in Preparation of a Gene Replacement Therapy Trial
Zobor D, Werner A, Stanzial F, Benedicenti F, Rudolph G, Kellner U, Hamel C, Andreasson S, Zobor G, Strasser T, Wissinger B, Kohl S, Zrenner E; for the RD-CURE Consortium (2017)
PURPOSE: The purpose of this study was to clinically characterize patients with CNGA3-linked achromatopsia (CNGA3-ACHM) in preparation of a gene therapy trial. METHODS: Thirty-six patients (age 7-56 years) with complete (cACHM) or incomplete (iACHM) CNGA3-ACHM were examined, including detailed psychophysical tests, extended electrophysiology, and assessment of morphology by fundus autofluorescence and spectral-domain optical coherence tomography […]
Gene therapy as a treatment concept for inherited retinal diseases (Ophthalmologe 112:720-7)
Bellingrath JS, Fischer MD (2015)
BACKGROUND: Gene therapy for inherited retinal diseases (IRDs) is currently being validated in several clinical trials and is becoming a promising therapeutic option for these previously incurable diseases. OBJECTIVES: The aim of this review is to give an overview of the concept, the application and the challenges associated with gene therapy. In particular, the pertinence […]
Retinitis pigmentosa: impact of different Pde6a point mutations on the disease phenotype (Hum Mol Genet 24:5486-99)
Sothilingam V, Garcia Garrido M, Jiao K, Buena-Atienza E, Sahaboglu A, Trifunović D, Balendran S, Koepfli T, Mühlfriedel R, Schön C, Biel M, Heckmann A, Beck SC, Michalakis S, Wissinger B, Seeliger MW, Paquet-Durand F (2015)
Mutations in the PDE6A gene can cause rod photoreceptors degeneration and the blinding disease retinitis pigmentosa (RP). While a number of pathogenic PDE6A mutations have been described, little is known about their impact on compound heterozygous situations and potential interactions of different disease-causing alleles. Here, we used a novel mouse model for the Pde6a R562W […]
Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa (Hum Mol Genet 23: 514-523)
Wert KJ, Sancho-Pelluz J, Tsang SH (2014)
Deficiencies in rod-specific cyclic guanosinemonophosphate (cGMP)phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre-clinical models with mutations in PDE6 have demonstrated that the photoreceptor cell survivalandvisual function can be rescued when the gene therapy virus is delivered into the subretinal space before the […]
Gene replacement therapy in achromatopsia type 2 (Klin Monbl Augenheilkd 231:232-40)
Mühlfriedel R, Tanimoto N, Seeliger MW (2014)
Achromatopsia is an autosomal recessive inherited retinal disease caused by a complete loss of cone photoreceptor function. About 80 % of achromatopsia patients show mutations in the alpha or beta subunit (A3 and B3) of the cGMP controlled cation channel CNG (cyclic nucleotide-gated channel) of cone photoreceptors. Homologous to the human disease, CNGA3 deficient mice reveal […]
Restoration of cone vision in the CNGA3‐/‐ mouse model of congenital complete lack of cone photoreceptor function (Mol Ther 18: 2057‐2063)
Michalakis S, Mühlfriedel R, Tanimoto N, Krishnamoorthy V, Koch S, Fischer MD, Becirovic E, Bai L, Huber G, Beck SC, Fahl E, Büning H, Paquet-Durand F, Zong X, Gollisch T, Biel M, Seeliger MW (2010)
Congenital absence of cone photoreceptor function is associated with strongly impaired daylight vision and loss of color discrimination in human achromatopsia. Here, we introduce viral gene replacement therapy as a potential treatment for this disease in the CNGA3−/− mouse model. We show that such therapy can restore conespecific visual processing in the central nervous system […]