The Prusiner Laboratory
We are a world-class research facility focused on understanding
neurodegenerative diseases caused by protein misfolding. We are part
of the Institute for Neurodegenerative Diseases at the University of
California, San Francisco. Our primary focus is on prion diseases
(e.g., Creutzfeldt-Jakob Disease (CJD) and bovine spongiform
encephalopathy or "mad cow disease"), with the aim of understanding
the biological basis of these diseases, developing effective
diagnostics and therapeutics, and improving patient and food safety by
inactivating prions.
The Molecular Basis of Prion Disease
We are interested in the structure of the prion protein and how it
causes disease. Through methods such as spectroscopy, electron
microscopy, fiber diffraction and crystallization, we can learn about
the structure of the prion protein in its normal and disease-causing
form, and the transition between the two. Understanding this will
allow us to develop better diagnostic tools and therapeutics.
Diagnostics
The early symptoms of CJD and other prion diseases are not well
defined and are frequently confused with other less devastating
conditions. Consequently, by the time patients are diagnosed with
CJD, the disease has usually progressed and caused widespread brain
damage. We are engaged in an effort to develop a rapid and sensitive
test able to detect human prions in the earliest possible stages of
disease. Simply halting the progression of prion disease may not
restore lost central nervous system function, and therefore, a
clinical test for the earliest possible diagnosis is essential. A
preclinical diagnostic test is critical to the success of developing a
drug therapy for CJD and other prion diseases.
Therapeutics
We are developing novel therapeutics against prion diseases by
applying our molecular understanding of prion biology. We have
already identified several promising classes of prion inhibitors. Our
current work is optimizing these drugs and discovering new inhibitory
compounds that have novel modes of intervention. The knowledge gained
by our prion therapeutics efforts will undoubtedly provide valuable
insights into treating other protein misfolding disorders.
Prion Inactivation
Infectious prions bind tightly to stainless steel surfaces and are not
inactivated by standard hospital sterilization techniques. Reuse of
contaminated surgical instruments can lead to iatrogenic transmission
of CJD to subsequent patients. Similarly, instruments used in
processing of prion-infected animals for food could spread infectivity
to prion-free meat if they are not properly decontaminated. We are
developing methods to inactivate prions, and validating them with
highly sensitive transgenic models.
