University of California

Forschungszentrum Juelich Gmbh

Unversität Zürich

Heinrich-heine-universitaet

Universit&auml;t Z&uuml;rich

Centre Suisse D'electronique Et De Mictotechnique Sa

Carsten Korth

Bruno Oesch

Markus Moser

Dieter Willbold

Susanne Aileen Funke

Beat Stierli

Stanley B Prusiner

Vishwanath R Lingappa

Rino Ernst Kunz

Hans Sigrist

Oliver Bannach

J&uuml;rg D&uuml;bendorfer

Peter Stregt

Kateryna Kravchenko

Hui Gao

Andreas Mueller-Schiffmann

Verian Bader

Peter Streit

Eva Birkmann

Steffen Huebinger

The invention concerns a method for detecting indicators for determining diseases (disease indicators), in which aggregates of misfolded proteins play a role, and a method for selective quantitation and/or characterization of these disease indicators.

Method for detecting indicators for determining diseases

A composition includes D-peptides or antibodies to at least one of to prevent a disease and to treat the disease, wherein the D-peptides interact with an amyloid peptide and the antibodies bind to both the D-peptide and the amyloid peptide.

Composition for producing anti-amyloid beta peptide antibodies with D-peptides

Methods of preparing monoclonal antibodies that differentially bind to a single conformer of a protein of interest are described. Passive immunization using these antibodies as well as use of conformer-specific antibodies as diagnostic reagents for the purpose of stratification of patient populations with regards to disease outcome, drug efficacy or drug sensitivity is also disclosed as well as active immunization with the protein conformer. In the screening techniques, detection can be for example by tissue immunostaining, western blotting or solution IP. A specific mab termed 7VC which shows conformation specificity to CtmPrP, a prion protein conformer that triggers neurodegeneration under specific assay conditions of pH and copper concentration, is described. A second specific antibody termed 19B10 shows conformation specificity for NtmPrP, a prion protein conformer that downregulates total PrP expression and effects cell differentiation.

Use of monoclonal antibodies to distinguish protein conformational isoforms

The presented invention relates to monoclonal antibodies useful in sensitive and specific immunological assays for the identification of prions in various tissues and body fluids, the production of such monoclonal antibodies by means of immunization of PrPmice by means of a new recombinant fragment of PrP and the use of the antibodies, e.g. for therapeutic and preventive treatments of humans and animals suffering from prion diseases.

Immunological detection of prions

The present invention provides a novel PrP protein, and nucleic acids encoding this protein, where the PrP protein is characterized in vivo by 1) incomplete glycosylation relative to glycosylation of wild-type PrP and 2) proper cellular localization, i.e. an ability to be transported to the cell surface. This novel, under-glycosylated PrP, unlike its normal cellular counterpart, can easily be converted into a protease-resistant isoform by incubation with infectious prions. The invention further provides systems for the study of prion disorders and methods of using these systems, e.g. the study of the mechanical processes in progression of prion-mediated disease or the identification of new therapeutic agents for treatment of prion-mediated disorders. In such systems, protease-resistant under-glycosylated PrP is generated de novo and can be detected by standard immunoblot techniques.

Models of prion disease

The presented invention relates to monoclonal antibodies useful in sensitive and specific immunological assays for the identification of prions in various tissues and body fluids, the production of such monoclonal antibodies by means of immunization of PrP mice by means of a new recombinant fragment of PrP and the use of the antibodies, e.g. for therapeutic and preventive treatments of humans and animals suffering from prion diseases.

This document describes an optical sensor unit and a procedure for the specific detection and identification of biomolecules at high sensitivity in real fluids and tissue homogenates. High detection limits are reached by the combination of i) label-free integrated optical detection of molecular interactions, ii) the use of specific bioconstituents for sensitive detection and iii) planar optical transducer surfaces appropriately engineered for suppression of non-specific binding, internal referencing and calibration. Applications include the detection of prion proteins and identification of those biomolecules which non-covalently interact with surface immobilized prion proteins and are intrinsically involved in the cause of prion related disease.

Optical sensor unit and procedure for the ultrasensitive detection of chemical or biochemical analytes

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Duesseldorf, Germany

Carsten Korth