Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial Recruitment: Year 1
Autor: | William W. Hauswirth, Fawzi Abukhalil, Vittorio Porciatti, William J. Feuer, Byron L. Lam, John Guy |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Male
Retinal Ganglion Cells Pathology Visual acuity genetic structures Genetic enhancement DNA Mutational Analysis Nerve fiber layer Visual Acuity Polymerase Chain Reaction chemistry.chemical_compound Nerve Fibers Child Aged 80 and over medicine.diagnostic_test Dependovirus Middle Aged medicine.anatomical_structure Female medicine.symptom Tomography Optical Coherence Adult Mitochondrial DNA medicine.medical_specialty Heterozygote Adolescent Genetic Vectors Molecular Sequence Data Optic Atrophy Hereditary Leber Retinal ganglion Asymptomatic DNA Mitochondrial Article Ophthalmology medicine Electroretinography Humans Point Mutation Amino Acid Sequence Aged business.industry Patient Selection Retinal NADH Dehydrogenase Genetic Therapy eye diseases chemistry sense organs Visual Fields business |
Popis: | To describe the patient profiles of the Leber hereditary optic neuropathy (LHON) Gene Therapy Clinical Trial, year 1. This study aims to identify and characterize affected patients and carriers with the G11778A mutation in mitochondrial DNA for planned gene therapy that will use "allotopic expression" by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous.Patients with LHON with visual loss as well as asymptomatic maternally related family members were molecularly screened for ND1, ND4, and ND6 mutations in mitochondrial DNA commonly associated with LHON. All patients and maternal relatives also underwent complete neuro-ophthalmic examination, automated visual field testing, pattern electroretinogram (PERG), and OCT3.Twenty-five subjects with LHON and 21 carriers positive for the G11778A mitochondrial DNA mutation were recruited. Three additional mutations in the ND4 gene, G11719A, G11947A, or G11914A, were detected. Mean retinal nerve fiber layer (RNFL) thickness was 78.3 μm up to 32 months after visual loss. It was 63.5 μm for all affected patients and 100.7 μm for carriers (P.01). Mean PERG amplitude was lower in affected patients (40% of normal) than in carriers (94% of normal) (P.01). Four carriers with PERG amplitudes less than 75% of normal had Early Treatment Diabetic Retinopathy Study acuity more than 20/25, mean defect more than -2 dB, and average RNFL thickness more than 80 μm.Potential candidates for future gene therapy may include affected patients, as late as 32 months after loss of vision, with mildly reduced RNFL thickness or carriers with low PERG amplitudes and normal RNFL thickness, if the PERG amplitude is a predictor of conversion to LHON in these carriers. |
Databáze: | OpenAIRE |
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