Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study

Campochiaro, Peter A.; Lauer, Andreas K.; Sohn, Elliott H.; Mir, Tahreem A.; Naylor, Stuart; Anderton, Matthew C.; Kelleher, Michelle; Harrop, Richard; Ellis, Scott; Mitrophanous, Kyriacos

doi:10.1089/hum.2016.117

Cited by 153 publications

(103 citation statements)

References 39 publications

(37 reference statements)

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“…A few mild and self-resolving subconjunctival and retinal hemorrhages were also observed (Rakoczy et al, 2015) as well as a case of acute endophthalmitis which resolved under antibiotic treatment (Schwartz et al, 2015). An intraoperative macular hole has been reported as well (Campochiaro et al, 2017). In contrast to IVT injections, the amount of currently available data on complications in SR injections is too limited in order to reliably estimate the complication rates.…”

Section: Subretinal Injectionmentioning

confidence: 89%

Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical Trials

2017

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An exceptionally high number of monogenic disorders lead to incurable blindness, making them targets for the development of gene-therapy. In order to successfully apply therapeutic vector systems in vivo, the heterogeneity of the disease phenotype needs to be considered. This necessitates tailored approaches such as subretinal or intravitreal injections with the aim to maximize transduction of target cell populations, while minimizing off-target effects and surgical complications. Strategic decisions on parameters of the application are crucial to obtain the best treatment outcomes and patient safety. While most of the current retinal gene therapy trials utilize a subretinal approach, a deeper understanding of the numerous factors and considerations in choosing one delivery approach over the other for various ocular pathologies could lead to an improved safety and treatment efficacy. In this review we survey different vector injection techniques and parameters applied in recent retinal (pre-)clinical trials. We explore the advantages and shortcomings of each delivery strategy in the setting of different underlying ocular pathologies and other relevant factors. We highlight the potential benefits for patient safety and efficacy in applying those considerations in the decision making process.

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Section: Subretinal Injectionmentioning

confidence: 89%

Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical Trials

2017

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“…Lentiviral vectors are being used for the treatment of patients with neovascular age-related macular degeneration (RetinoStat ® , Oxford BioMedica, UK) (32,33), Usher syndrome (UshStat ® , Sanofi, France) (34,35) and Stargardt disease (EIAV-ABCA4 [SAR422459], sanofi, France) (12,13). …”

Section: Retinal Gene Therapymentioning

confidence: 99%

Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

et al. 2019

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Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.

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“…[7,11] Although the full pathogenesis has not been elucidated, current (and experimental) treatments have attempted to address the local inflammation in order to decrease the progression of vision loss (Table 2). [11,162,167] …”

Section: Ocular Diseasesmentioning

confidence: 99%

“…[162] Moreover, many patients required frequent injections (sometimes every six weeks) for a prolonged period of time to prevent vision loss. [167] In order to avoid these side effects, gene therapies for AMD have been explored as ways to enable effective suppression of the VEGF pathway. [167,176] …”

Section: Ocular Diseasesmentioning

confidence: 99%

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Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Ratay

Bellotti

Gottardi³

et al. 2017

Adv Healthcare Materials

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Dry eye disease (DED), age-related macular degeneration (AMD), and Uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, pro-inflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies have been developed to either address the symptoms or abate the underlying cause of these diseases. Herein, we will review the challenges to deliver drugs to the relevant location in the eye for each of these diseases as well as current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.

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Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study

Cited by 153 publications

References 39 publications

Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical Trials

Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical Trials

Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

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