An inhibitor to the ß-secretase pathway of Aß generation in Alzheimer´s Disease

Invention Antibodies have been raised against the β-secretase cleavage site in Amyloid β precursor protein (AβPP). These antibodies can prevent the processing of AβPP and the subsequent formation of amyloid deposits, a central event in the pathogenesis of Alzheimer’s Disease. This approach will not interfere with 'house keeping' activities associated with β-secretase, likely to be a problem with direct β-secretase inhibitors. Therapy may be active, inducing the patient's immune system to produce antibodies to the epitope defining the β-secretase cleavage site, or passive, via treatment with antibodies engineered to cross the BBB
The Need Alzheimer's disease affects more than 4 million individuals in the US alone. Its prevalence is increasing with increased longevity together with the influence of the baby-boom generation. With current medications providing only minimal relief from disease symptoms and failing to substantially alter the course of the disease, Alzheimer's disease represents a major health care burden. Agents to prevent or alter the course of the disease are desperately needed.
Potential Applications o Alzheimer's disease prophylaxis to prevent establishment of the disease

o Alzheimer's disease therapy to alter the course of the disease
Advantages o Highly specific to AD pathology

o Expected to be safer and less toxic than β-secretase inhibitors

o Intracellular activity expected minimizes inflammatory response to passive immunotherapy

o Therapy targets both the normal β-secretase cleavage site and the mutated site found in the “Swedish” familial AD mutation, which causes early–onset AD

o Antibodies are engineered for good BBB penetration and maintenance of the antigen binding domain
Stage Tissue culture studies with AβPP –over-expressing cells show that antibodies to the β-secretase cleavage site epitope block Aß generation from its AβPP precursor.

Active immunization of AD transgenic mice show, reduction in intracellular and extracellular Aß and the amyloid burden, as well as considerable reduction in microglia activation and concomitantly great improvement in cognitive functions
Patent Pending Tech Transfer Officer Ms. Irit Ben-Chlouch Office: +972-3-6406601 Fax: +972-3-6406675 Mail: [email protected]

Inventor(s): Beka Solomon

Type of Offer: Licensing



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