An Effective Sema3A Antibody as a Therapy for Optic Nerve Neurodegenerative Diseases
Glaucoma and ischemic or neuro-degenerative diseases of the optic nerve lead to vision loss and blindness. These pathologies are associated with progressive apoptosis of the retinal ganglion cells (RGC), a process which involves expression of Semaphorin 3A protein in the axonal guidance pathways. The identified Sema3A antibody provides a potentially innovative therapeutic tool for these uncured pathologies.
Non-arthritic ischemic optic neuropathy (NAION), an FDA recognized orphan disease and other optic nerve neurodegenerative diseases (glaucoma, retinal detachment), pose a huge global burden of vision loss and blindness with very limited cure available. The proposed mode of action of Sema3A antibody identifies a potential novel therapy to fill the gap.
A newly identified Semaphorin3A antibody blocks the active site of the protein and consequently mitigates the apoptotic RGC death process. This new tool may provide a new cure for the optic nerve neurodegenerative pathologies.
ADVANTAGES OVER EXISTING TECHNOLOGIES:
• No existing treatment for NAION
• Retinal detachment is treated via surgery with poor recovering results as time is of essence as retinal ganglion cells are lost until surgery is performed. An injection of anti-Sema3A antibody Intra ocular injection can be performed immediately after the assault.
• A newly diagnosed Glaucoma patient could be treated immediately and prevent further loss of retinal ganglion cells.
• The International Glaucoma Society presented in September 2020, the need of neuro-protecting treatment as complementary to the current treatment of lowering the intra ocular pressure (IOP).
• A newly identified Sema3A antibody (3H4) witch blocks RGC apoptotic cascade.
• The specific and efficient activity of the antibody was proven in-vitro in an Axon Repulsion Assay.
• In-vivo proof of concept was based on several models: axotomy in rats, retinal detachment in rats, acute glaucoma in rabbits and non-arthritic ischemic optic neuropathy (NAION) (a new in house developed model) in rabbits.
• Treatment with Sema3A antibody saved 45-52% of the RGC in all models tested.
•No toxic effect or inflammatory reaction were detected following antibody injection
PCT PCT/IL2020/050717 (was submitted in June 2020): SEMAPHORIN 3A NEURODEGENERATION MODULATORS: ANTIBODIES AND USES THEREOF