Promising First Steps in Gene Therapy for Choroideremia

Huckfeldt, Rachel M.; Bennett, Jean

doi:10.1089/hum.2014.2503

Cited by 4 publications

(5 citation statements)

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“…As gene augmentation clinical trials have started in CHM, 6,9,[13][14][15]17,78,79 it becomes important that molecular testing be available to any patient with a CHM-like phenotype and that the CHM phenotype be thoroughly characterized. Defining the phenotype as a function of time is important to accurately stage the disease process and understand outcomes.…”

Section: What Is the Clinical Relevance Of The Current Results?mentioning

confidence: 99%

“…[8][9][10] Lessons learned from the early GT studies 8 highlight the important role of patient selection and choosing the right outcome measures in order to understand better the short-and long-term results of trialed interventions. As clinical trials of gene therapy for CHM have been initiated, 9,[11][12][13][14][15][16][17] a better understanding of the structural and functional changing features of the CHM-retina is needed. In the present study, a large cohort of men affected with molecularly proven CHM was characterized with noninvasive tests, including cross-sectional data and serial measurements, to gain insight into the disease's natural history.…”

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confidence: 99%

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Visual Function and Central Retinal Structure in Choroideremia

Hèon

Alabduljalil

McGuigan

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Section: What Is the Clinical Relevance Of The Current Results?mentioning

confidence: 99%

mentioning

confidence: 99%

Visual Function and Central Retinal Structure in Choroideremia

Hèon

Alabduljalil

McGuigan

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…33-34 Confirmation of safety and efficacy in these new trials will help establish gene therapy as a treatment approach for CHM and other inherited retinal degenerations. 29,35,36 Although several groups have initiated clinical trials for various inherited retinopathies including CHM (clinicaltrials.gov), there remain gaps in our understanding of their natural history.…”

Section: Introductionmentioning

confidence: 99%

Natural History of the Central Structural Abnormalities in Choroideremia

et al. 2017

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Purpose To describe in detail the central retinal structure of a large group of patients with Choroideremia (CHM). Design prospective, cross-sectional, descriptive study. Subjects Patients (n=97, age 6-71 years) with CHM and subjects with normal vision (n=44; ages 10-50 years) were included. Methods Subjects were examined with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n=24) with automated static perimetry within the central regions (±15°) examined with SD-OCT. Main outcome measures VA and visual thresholds, total, inner and outer nuclear layer (ONL) thicknesses, and the horizontal extent of the ONL and of the photoreceptor outer segment (POS) interdigitation zone. Results Earliest abnormalities in regions with normally appearing RPE were the loss of the POS and EZ zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, non-atrophic retina in the majority (69%) of patients. In general, retinal pigment epithelium (RPE) abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning. Conclusions Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until late disease. TZ migration to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.

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“…Over the past 20 years, remarkable results have been obtained with gene therapy in the treatment of hemophilia [97], cystic fibrosis [98], and different types of hereditary blindness [99][100][101]. For other inherited disorders the potential beneficial effect of gene therapy is being investigated in preclinical studies and clinical trials, for example, in immunodeficiency [102] and a variety of neurological disorders [103].…”

Section: Gene Therapymentioning

confidence: 99%

“…Gene therapy is promising for patients with inherited renal disorders; however, the method is developing slowly because of variable gene transduction efficiency, difficult delivery at specific sites in the kidney, and generally reported adverse effects after use of adenoviruses and retroviruses [104][105][106][107][108]. Also, its use has been reported to be safe and effective in various clinical trials [97][98][99][100][101]106,109]. Also, its use has been reported to be safe and effective in various clinical trials [97][98][99][100][101]106,109].…”

Section: Gene Therapymentioning

confidence: 99%