Vision - Prolonged inhibition of semaphorin3a pathway via a bio-degradable implant towards a better therapy for visual sensory impairments
Project Budget: 5,661,253
Coordinator: Prof. Arieh Solomon, TAU
Glaucoma is a term which covers different pathological conditions leading to neuropathy, degeneration of the vulnerable optic nerve axons and cell bodies (Retinal Ganglion Cells , RGC). The most common glaucoma is associated with high intraocular pressure (IOP). The treatment today is based on lowering the IOP but is inefficient in preventing RGC loss. Thus there is an urgent need for novel treatment.
Semaphorin 3A (Sema3A) is a cell secreted protein that participates in the axonal guidance pathways. Partner TAU was the first to show that Sema3A is also capable of inducing neuronal cell death. Importantly, marked inhibition of RGC loss was achieved when eyes with axotomized optic nerves were co-treated by intravitreous injection of antibodies against Sema3A providing the proof of concept for the therapeutic approach for neuroprotection via inhibiting the Sema3A pathway. This concept was further validated by partner CSIC who developed a small molecular weight peptoid inhibitor (SICHI) of Sema3A and showed that this inhibitor promotes neural regeneration of damaged axons. Many of the pathological mechanisms in glaucoma are apparent in acute optic nerve neuropathy which is characterized by neuronal death following stroke (an age related disease).
Thus, this project goal is to develop a therapy for glaucoma and acute optic nerve neuropathy using the same therapeutic approach, i.e. inhibiting further death of vision related neural cells by prolonged inhibition of Sema3A apoptotic pathway. The therapy will be based on a minimally invasive implant for controlled release of novel therapeutic moieties. Thus, the project will develop two Sema3A inhibitors: a low MW compound and a Sema3A targeted antibody. These inhibitors will be loaded into a novel controlled and prolonged release minimal invasive, injectable implant.
TelAviv University (TAU)
Nicast Ltd (NIC)
Synovo GmbH (SYN)
Institute for Advanced Chemistry of Catalonia (CSIC)
Anaxomics Biotech, S.L (AX)