TARGETAMD

"Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (AMD)"

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 Obiettivo del progetto (Objective)

'Age-related Macular Degeneration (AMD), a neurodegenerative disease of the retina, is a major cause of blindness in elderly people. Due to the aging population, AMD has been referred to as a “time bomb” in society. In the exudative form of AMD, high levels of vascular endothelial cell growth factor (VEGF) and low levels of pigment-epithelial derived factor (PEDF), an inhibitor of vascularization and a neuroprotective factor produced by retinal pigment epithelial (RPE) cells result in subretinal neovascularization and retinal pigment cell degeneration. The current treatment by monthly injections of anti-VEGF antibodies is only effective for ~30% of patients. To avoid the severe side effects, high costs and the overall continuing burden on health care associated with monthly antibody injections, inducing a higher level of PEDF expression to inhibit neovascularization would be a viable therapeutic alternative. TargetAMD will subretinally transplant genetically modified, patient-derived, iris- or RPE cells that overexpress PEDF to provide a long-lasting cure of AMD. Stable PEDF gene delivery will be based on the non-viral Sleeping Beauty transposon system, which combines the efficacy of viral delivery with the safety of naked DNA plasmids. Academic scientists and SME partners will produce innovative gene delivery technologies, reagents and devices to be translated into a simple and safe gene therapeutic treatment for exudative AMD. Experienced clinicians will perform two clinical trials, comprising isolation and PEDF-transfection of a patient’s pigment epithelial cells and implantation of transfected cells into the patient during a single, 60-minute surgical session. This project will bring a significant enhancement on quality of life to AMD patients, highlight the synergistic power of academic, clinical and industrial cooperation to the scientific arena, and open new markets for novel products for clinical applications of transposon-based gene therapy to industry.'

Introduzione (Teaser)

A European study has designed an innovative therapeutic strategy for treating retinal degeneration. It is based on the delivery of a gene that will inhibit the pathological formation of new vessels in the eye.

Descrizione progetto (Article)

Age-related macular degeneration (AMD) is a chronic progressive condition that results from age-related alterations in the retina. There are two types of AMD: a slow-progressing, non-vascular form and a rapidly progressing, blinding form. In the latter, high levels of vascular endothelial cell growth factor (VEGF) and low levels of pigment epithelium-derived factor (PEDF), an inhibitor of vascularisation, have been observed.

Based on this, current treatment consists of monthly injections of anti-VEGF antibodies or inhibitors. However, the high cost and low efficacy of this approach have prompted researchers to suggest that increasing the levels of PEDF should be a viable therapeutic alternative.

Research teams on the EU-funded 'Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (AMD)' (http://www.targetamd.eu/ (TARGETAMD)) project propose to transplant genetically modified cells that overexpress PEDF as a long-lasting cure for AMD. The procedure entails introduction of the human PEDF gene into autologous retinal pigment epithelial and iris pigment epithelial cells ex vivo, and transplantation into the sub-retinal space of AMD patients. For this purpose, they are using the non-viral Sleeping Beauty transposon system that has the capacity to integrate into the host cell's genome.

The overall aim of the TARGETAMD study is to develop this transposon-based strategy into a clinically suitable modality. Cells have thus been isolated from biopsies and the transfection conditions have been optimised. Ongoing activities concentrate on the evaluation of the method in suitable small animal models of AMD.

TARGETAMD partners are confident that the major challenge of the procedure, which is associated with the small number of isolated retina cells, has been successfully addressed. As a result, they express their optimism that a phase Ib/IIa clinical trial for the treatment of AMD using genetically modified autologous cells will revolutionise disease outcome.