Duke University

Warren J Strittmatter

Allen D Roses

Donald E Schmechel

Jan J Enghild

Guy S Salvesen

William D Matthew

J Brice Weinberg

Catherine R Gutman

James R Burke

Jeffery M Vance

Karl H Weisgraber

Michel Goedert

Dmitry Y Goldgaber

Yoshitaka Nagai

David Huang

Ann M Saunders

Provided herein are methods for identifying a subject afflicted with chronic lymphocytic leukemia who is responsive to treatment with a chemotherapeutic agent by detecting the presence or absence of at least one APOE4 allele in the subject, the presence of an APOE4 allele identifying the subject as responsive to the treatment. Also provided are methods of treating a subject afflicted with chronic lymphocytic leukemia, including administering an estrogenic agent, an androgen withdrawal agent, an apoE4 peptide or mimetic thereof, and/or a chemotherapeutic agent in an amount effective to treat said chronic lymphocytic leukemia. Methods of determining a prognosis for a patient diagnosed with chronic lymphocytic leukemia are also provided. In addition, methods for stratifying a subject into a subgroup of a clinical trial and methods for identifying a patient in a clinical trial of a treatment for chronic lymphocytic leukemia are herein provided.

Chronic lymphocytic leukemia prognosis and treatment

Compounds that selectively bind to expanded polyglutamine repeats are disclosed. Such compounds are characterized in that they bind to a first polyglutamine peptide consisting of 60 glutamine residues under conditions in which they do not bind to a second polyglutamine peptide consisting of 20 glutamine residues. Conjugates of such compounds, nucleic acids encoding the same, and methods of use thereof are also disclosed.

Compounds that selectively bind to expanded polyglutamine repeat domains and methods of use thereof

A method for detecting the binding of a test compound to a probe molecule comprises providing a test compound, the test compound having a first fluorophore bound thereto, and providing a screening substrate. The screening substrate comprises a solid support, a probe molecule bound to the solid support, and a second fluorophore bound to the solid support adjacent the probe molecule. An advantage of the invention is that this obviates the need for binding the second fluorophore directly to the probe molecule. Preferably, the second fluorophore is bound to the solid support by a flexible linker group. This enables the second fluorophore to interogate different positions on the probe molecule, which is also bound to the solid support adjacent the linker group, enhancing the ability of the method of the invention to detect positive binding events (specific binding of the test compound to the probe molecule. The first and second fluorophores together comprise the donor and acceptor fluorophores of a fluorescence resonance energy transfer (FRET) pair, or a &ldquo;donor/acceptor pair.&rdquo; The test compound is contacted to the screening substrate, and the screening substrate illuminated with light at a wavelength that is absorbed by the donor fluorophore. The transfer of energy from one to the other fluorophore is then detected, with the transfer of energy indicating the binding of the test compound to the probe. Substrates useful for carrying out the foregoing methods are also disclosed.

Method of screening for specific binding interactions

Provided herein are compositions comprising complexes of apolipoprotein E and ciliary neurotrophic factor. The apolipoprotein E can be any isoform, but is preferably apolipoprotein E3. Also preferred are covalent complexes of apolipoprotein E and ciliary neurotrophic factor, more preferably those formed by intermolecular disulfide bonds between cysteine residues. Further provided are methods of enhancing the survival of neural cells by administering a composition comprising a complex of apolipoprotein E and ciliary neurotrophic factor. The claimed methods can be carried out both in vitro and in vivo.

Complexes of apolipoprotein E and ciliary neurotrophic factor (CNTF) and methods of use

The present invention relates to the finding that antibodies bind to the &bgr;-amyloid peptide, and that &bgr;-amyloid peptide binds the hinge region of the immunoglobulin heavy chain, thereby preserving the ability of the immunoglobulin to bind antigen. Methods for binding compounds such as detectable groups to &bgr;-amyloid peptide are accordingly presented.

Method of binding material to the &bgr;-amyloid peptide

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is afflicted with Alzheimer's disease or at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Methods of detecting Alzheimer's disease

A method of combatting Alzheimer's disease which comprises increasing the binding of the tau protein in nerve cells of that subject, and/or the binding of MAP2c protein in nerve cells of that subject, to either Apolipoprotein E or an Apolipoprotein E fragments capable of binding tau and/or MAP2c. In one embodiment, the method comprises administering the ApoE or ApoE fragment to the subject; in another embodiment, the method comprises administering to the subject a vector capable of entering nerve cells, which vector then upregulates the expression of an ApoE or an ApoE fragment capable of binding tau and/or MAP2c in nerve cells. Compositions useful for carrying out these methods are also disclosed.

Methods and compositions for binding tau and MAP2c proteins

Apolipoprotein E isoform-specific monoclonal antibodies

GAPDH binds to expanded polyglutamine regions which are found in proteins encoded by genes with CAG repeat domains, which genes cause inherited neurodegenerative disorders and are associated with certain psychiatric disorders. Therapeutic methods are based on inhibiting the binding of GAPDH to expanded polyglutamine regions. A method of screening compounds for the ability to inhibit binding of GAPDH to polyglutamine regions is described.

Method to screen compounds that affect GAPDH binding to polyglutamine

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Kit for detecting the ApoE4 allele, and for diagnosing the existence or

Peritoneal fluid and peritoneal wash fluid provide a source of abundant apolipoprotein E. Methods for isolating apolipoprotein E from peritoneal fluid or peritoneal wash fluid are provided.

Source of apolipoprotein E and method of isolating apolipoprotein E

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA, encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is afflicted with Alzheimer's disease or at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Methods of screening for Alzheimer's disease

An apparatus for performing a spinal puncture on a subject to obtain a sample of cerebrospinal fluid is disclosed. The apparatus operates at ambient pressure. The spinal puncture apparatus is designed to interface with a sample container. A sample container apparatus is also disclosed, as is a kit for use in performing spinal puncture on a subject to obtain a sample of cerebrospinal fluid.

Growing community of inventors

Durham, NC, United States of America

Warren J Strittmatter