Methods for increasing endogenous levels of...

A - Human Necessities – 61 – K

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A61K 38/22 (2006.01) G01N 33/53 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2244864

Levels of free corticotropin-releasing factor (CRF) or CRF-related peptide are increased by administration to a patient of a ligand inhibitor of a CRF/CRF- binding protein complex or CRF-related peptide/CRF-binding protein complex. The ligand inhibitor binds to CRF-binding protein, thereby causing the release of CRF or increasing the level of the CRF-related peptide. The ligand inhibitor may be a peptide derived from CRF or a related protein or a non- peptide. Administration of the ligand inhibitor may provide improvement in learning and memory, in decreasing food intake or in providing treatment for diseases associated with low levels of CRF in the brain, notably Alzheimer's disease. A method is also provided for screening compounds to select particularly effective CRF antagonists for in vivo administration to mammals.

On augmente les niveaux du facteur de libération des corticotropines (CRF) ou du peptide associé au facteur CRF en administrant à un patient un inhibiteur ligand d'un complexe du facteur CRF/protéine de liaison du facteur CRF ou d'un complexe du facteur CRF-peptide associé/protéine de liaison du facteur CRF. Cet inhibiteur se fixe sur la protéine de liaison du facteur CFR, provoquant ainsi la libération du facteur CRF ou accroissant la concentration du peptide associé à ce facteur. L'administration de cet inhibiteur peut apporter une amélioration dans les domaines de l'apprentissage et de la mémoire, de la diminution de l'apport alimentaire ou dans le traitement des maladies associées à des concentrations basses du facteur CRF dans le cerveau, notamment dans la maladie d'Alzheimer. On décrit également un procédé de criblage de composés afin de choisir notamment des antagonistes efficaces du facteur CRF, en vue d'une administration in vivo de ceux-ci à des mammifères.

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