Neurodegenerative Diseases

Structural Neurology:  A New Approach to the Understanding, Treatment and Prevention of Neurologic Disorders

The rapid aging of the population in most developed countries will eventually produce a world in which almost a third of its inhabitants will be over 60 years of age.  Coincidentally, 60 is the age at which the incidence of neurodegenerative diseases such as Parkinson’s Disease, Alzheimer’s Disease and stroke begin to rise exponentially.  Effective treatments are lacking for these and nearly all of the major neurologic disorders, which taken together cost the U.S. over $330 billion per year.  We have set up a program to bring the techniques of structure-guided drug discovery to bear on a number of these diseases.  The program combines human genetics, studies in model organisms, mechanistic enzymology, computational approaches, and X-ray crystallography of validated targets to provide novel therapeutic approaches.  One highlight of our strategy is the use of pharmacological chaperones to increase the steady-state concentration of neuroprotective proteins; thus, we are not only limited to finding inhibitors of neurotoxic ones.   We have already had some preliminary success applying this approach in the treatment of Gaucher Disease and the prevention of Parkinson’s and Alzheimer’s Diseases.