Lead Inventor: Ottavio Arancio, M.D., Ph.D. The Challenge/ Problem/ Unmet Need: Alzheimer's disease (AD) is the 7th leading cause of death, it was responsible for 65,829 deaths in the U.S. in 2004 and this number continues to rise. At over $100 B per...

Lead Inventor: Ottavio Arancio, M.D., Ph.D.

The Challenge/ Problem/ Unmet Need:
Alzheimer's disease (AD) is the 7th leading cause of death, it was responsible for 65,829 deaths in the U.S. in 2004 and this number continues to rise. At over $100 B per year, AD is the 3rd most costly disease in the U.S., after heart disease and cancer, and there are an estimated 24 million people with dementia worldwide.
According to the "amyloid hypothesis", the amyloid plaques in the brain are responsible for the pathology of Alzheimer's disease. It was shown that these plaques consist of aggregated polypeptide of ~39-42 amino acids, which are known as amyloid-beta (Ab) peptides. Abnormally high levels of Ab are toxic and have been shown to cause synaptic dysfunction and memory loss.
However, Ab is normally produced in the brain, where the in vivo concentration in the brain has been estimated to be in the range of 200-1000pM. Despite the presence of Ab throughout life in normal individuals, it is not known whether Ab has a physiological role in the brain.

Details of the Invention:
The present invention provides a surprising discovery that administration of Ab42 at a concentration approximately equal to its physiological levels (200pM) enhances both long term potentiation (LTP), a widely studied cellular model of learning and memory, as well as memory in animal behavior experiments. The invention provides for methods that enhance synaptic plasticity and memory by administering to a subject's brain an effective amount of amyloid beta peptide, such as Ab42. Additionally, the invention demonstrates that acute, antibody-mediated depletion of the endogenously produced Ab dramatically interferes with LTP in vitro and memory in vivo.
Based on these findings, the invention provides that Ab itself is a critical positive-modulator of memory at physiological concentrations within the normal central nervous system.

Applications:
• Memory disorders, which comprise or are associated with neurodegenerative diseases such as: Alzheimer's disease, Parkinson's disease, Down's Syndrome, Hungtington's disease, etc.
• The invention could also provide means to enhance subject's normal memory

Advantages:
• The invention opens a new way to use drugs that mimic Ab structure, or are targeted to the receptor(s), including alpha7-nicotinic acetylcholine receptors, through which Ab acts under normal physiological conditions, to enhance memory
• The invention is based on administering compound that is naturally present in the brain (Ab peptide itself) or Ab derivatives
• This discovery gives a new perspective on development of drugs that interfere with Ab production (these drugs are being developed by other groups to fight AD), because these drugs might have a negative effect on memory instead of an improvement of memory deficit

Patent Status: Patent Pending

Licensing Status: Available for Licensing and Sponsored Research Support

Publication: Amyloid-beta peptide is critical for hippocampal LTP induction and memory acquisition. In: Society for Neuroscience Annual Meeting, Washington, DC. (2008)

Pat. Title: METHODS AND COMPOSITIONS FOR ENHANCING MEMORY METHODS AND COMPOSITIONS FOR ENHANCING MEMORY METHODS AND COMPOSITIONS FOR ENHANCING MEMORY

App. #: 60/850,734 11/870,724 12/185,396

Licensing or sponsored research support