University of California

Thomas L James

Stanley B Prusiner

Fred Ehrenkranz Cohen

Kiyotoshi Kaneko

Molecules are disclosed that interact with the cellular components involved in conversion of PrP to PrP . The molecules disclosed can be small molecules, peptides or protein analogs, e.g. analogs of PrP . In one embodiment, these molecules interfere with prion formation and/or replication, e.g. by preventing interactions of proteins involved in a prion complex or by interfering with &bgr;-sheet formation. In another embodiment, the molecules of the invention promote PrP conversion to PrP , e.g. by binding to PrP and facilitating a conformational change from PrP to PrP .

Inhibitors of prion formation

A protein designated Prion Protein Modulator Factor (PPMF) is disclosed which protein is an auxiliary factor in prion replication. PPMF is primarily characterized by its ability to bind to PrP.sup.C and facilitate a conformational change from PrP.sup.C to PrP.sup.Sc. A discontinuous epitope on PrP.sup.C comprising residues 172, 215 and 219 of human PrP.sup.C binds PPMF which is encoded by a nucleotide sequence derived from an organism selected from the group consisting of cow, sheep, mouse, hamster and human. In converting PrP.sup.C to PrP.sup.Sc the PPMF forms a PrP.sup.C /PrP.sup.Sc complex and is a rate limiting compound in the formation of that complex. Molecules, including antibodies, which bind PPMF or its epitope on PrP.sup.C are useful in the treatment of prion disease. Pharmacophores of the PrP.sup.C epitope are disclosed as are useful therapeutics and pharmacophores of the PPMF surface which binds PrP.sup.C. Animals resistant to prion disease are taught as are genes for producing such animals. Assay systems are disclosed which use PPMF to amplify PrP.sup.Sc is a sample being tested.

Growing community of inventors

Nicasio, CA, United States of America

Thomas L James