ENDE

Development of a cell-based Neuroprotective Treatment for Retinal Degeneration

Objectives

  • Generation of stable cell lines expressing neurotrophic factors or combinations thereof validated for their specific survival supporting effect in the first funding period of HOPE
  • Functional validation of cell lines producing candidate molecules in vivo after surgical implantation of to the retina of mice suffering from different forms of retinal degeneration
  • Generation and quality control of GMP-certified cells

Summary

The majority of rare forms of currently incurable inherited retinal degenerations (RD) are unlikely to become therapeutically targeted by gene therapy. Neuroprotection can provide a generic concept towards treating diverse forms of RD. We propose here that (i) retina-intrinsic neuroprotective molecules produced by Müller glial cells are used in order to minimize adverse effects and (ii) that experimentally selected combinations of such factors rather than a single neurotrophic factor shall be efficient to treat RD.
We have identified neurotrophic retinal Müller glial cell-derived factors and already characterized some of them in depth. We now aim at further validating these proteins for their efficacy against neuronal cell death in vivo. For sustained delivery in vivo, we will generate encapsulated cell lines stably overexpressing a cocktail of these novel retinal Müller glial cell-derived pro-survival factors. CellBeads® shall stably produce a synergistically acting set of experimentally verified pro-survival factors halting photoreceptor cell death in selected animal models for human RD after implantation. GMP qualified cell lines produced in collaboration with CellMed (SP6) will create a basis for translation of this approach towards clinical use. Clinical application of retinal Müller glial cell derived neuroprotective factors as biologicals or eventually biosimilars can provide a generic therapeutic strategy to treat multiple, genetically heterogeneous and rare forms of RD.