Drug Discovery

Neuroprotection

Alzheimer's Therapeutics: Neurotrophin Small Molecule Mimetics

Investigator(s): Frank Longo, M.D., Ph.D., Professor and Vice Chair

Institution(s): VAMC Neurology, University of California, San Francisco (UCSF), CA

Duration: 2000 - 2003

Summary:

In AD there is extensive degeneration of the brain cholinergic and other systems. A brain protein called nerve growth factor (NGF) has been shown to prevent loss of cholinergic neurons in animal models, including primates, and has been suggested as a possible treatment for AD. NGF is a protein and does not cross into the brain after peripheral administration. Clinical trials in AD patients using NGF are limited due to the difficulty in getting the protein into the brain. Therefore there is a need to find a safe and effective method of delivering it to brain tissue. Dr. Longo, an expert in NGF, proposes to develop small organic (non-peptide) compounds that mimic the effects of NGF but have the advantage of gaining entry into the brain. Specifically, Dr. Longo has developed prototype small peptide (intermediate-stage) drugs that act like NGF. Using the information on structure and activity that Dr. Longo has obtained from these intermediate-stage compounds he will screen libraries of small organic compounds for their ability to act like NGF.