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Prolonged inhibition of semaphorine3a pathway via a bio-degradable implant towards a better therapy for visual sensory impairments

Objective

The visual pathway is a component of the central nervous system (CNS) and therefore is not regenerative. Acute optic nerve injury, ischemic optic neuropathy and glaucoma are conditions that initially lead to partial blindness and eventually could lead to total blindness. Extensive neuron and retinal ganglion cells (RGC) death is evidenced in these pathologies. Semaphorin 3A (Sema3A) is a cell secreted protein that participates in the axonal guidance pathways. Partner TAU was the first to show that Sema-3A is also capable of inducing neuronal cell death. Elevated levels of Sema3A were than found in glaucoma. TAU further showed the viscous role of Sema3a that is mediating the vast RCG apoptosis following optic nerve injury. Importantly, marked inhibition of RGC loss was achieved when axotomized eyes were co-treated by intravitreous injection of antibodies against the Sema3A providing the proof of concept for the therapeutic approach to inhibit the Sema3A pathway following optic nerve injury. This concept was recently validated by partner SIC who developed a small molecule weight inhibitor of Sema3A and showed that this inhibitor promotes neural regeneration of damaged axons. Acute or chronic assault to neural cells create an immediate death of part of the population and a signal for further death of the remaining cells close to the damaged area. The project goal is to develop a therapeutic approach to stop further death of neural cells by providing prolonged inhibition of the apopototic pathway of Sema-3A using antibody targeted to this protein or a low MW inhibitor of sema3A. The Sema3A inhibitors would be constantly released from a novel intraocular biodegradable implant. The clinical efficacy of this approach will be evaluated in two common devastating pathologies: optic nerve injury and glaucoma.

Call for proposal

FP7-HEALTH-2012-INNOVATION-2
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Coordinator

TEL AVIV UNIVERSITY
Address
Ramat Aviv
69978 Tel Aviv
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 556 800
Administrative Contact
Lea Pais (Ms.)

Participants (4)

NICAST LTD
Israel
EU contribution
€ 1 294 320
Address
Yodfat 2 Northern Industraial Zone
71291 Lod
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
David Simhon (Dr.)
SYNOVO GMBH
Germany
EU contribution
€ 1 170 936
Address
Paul Ehrlich Str 15
72076 Tuebingen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Michael Burnet (Dr.)
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 1 173 037
Address
Calle Serrano 117
28006 Madrid
Activity type
Research Organisations
Administrative Contact
Alberto Sereno Alvarez (Mr.)
ANAXOMICS BIOTECH SL
Spain
EU contribution
€ 466 160
Address
Calle Diputacio 237, P 1 Pta 1
08007 Barcelona
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Mireia Coma (Dr.)