TargetAMD results in brief – www.cordis.eu

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 VEGF and low levels of PEDF, an inhibitor of vascularisation and potent neurotrophic factor, 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 demands a viable therapeutic alternative.

Research teams on the EU-funded ‘Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (AMD)’ project propose to transplant GMP-grade genetically modified cells that overexpress PEDF in a First-In-Man clinical trial as a life-long therapeutic solution for AMD. The personalised procedure entails introduction of the human PEDF gene into autologous 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.

Preclinical studies could be successfully accomplished proving consistency of a Gene Therapy Medicinal Product (GTMP) of highest quality and confirming safety and efficacy of the approach in vivo in 3 different species and models. Development and production of novel devices, reagents and plasmids have been successfully completed. In a recent Presubmission Meeting where the preclinical data was presented and discussed, the Swiss regulatory authority confirmed appropriateness of preclinical data toward the clinical trial.

Therefore, the TargetAMD partners are confident that the major challenge of the procedure, which is associated with the small number of isolated cells, has been successfully surmounted and are optimistic that the phase Ib/IIa clinical trial for the treatment of AMD using genetically modified autologous cells will revolutionise therapeutic outcome.