Novel method for down-regulation of amyloid

A - Human Necessities – 61 – K

Patent

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Details

A61K 38/17 (2006.01) A61K 39/00 (2006.01) C07K 14/435 (2006.01) C07K 14/47 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2400838

Disclosed are novel methods for combatting diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloidogenic proteins (proteins contributing to formation of amyloid) such as beta amyloid (A.beta.). Immunization is preferably effected by administration of analogues of autologous amyloidogenic polypeptides, said analogues being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous A.beta. which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the majority of A.beta.'s B-cell epitopes. Also disclosed are nucleic acid vaccination against amyloidogenic polypeptides and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic analogues of the amyloidgonic proteins, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

L'invention concerne de nouvelles méthodes permettant de lutter contre les maladies caractérisées par des dépôts d'amyloïde. Ces méthodes reposent de manière générale sur une immunisation contre les protéines amyloïdogènes (protéines contribuant à la formation d'amyloïde) telles que les protéines bêta-amyloïdes (A.beta.). On effectue de préférence cette immunisation par l'administration d'analogues de polypeptides amyloïdogènes autologues, ces analogues étant capables d'induire la production d'anticorps contre les polypeptides amyloïdogènes autologues. L'immunogène préféré est une protéine A.beta. autologue qui a été modifiée par l'introduction d'un seul ou de plusieurs épitopes de lymphocytes T étrangers, immunodominants et ubiquistes tout en préservant sensiblement la majorité des épitopes des lymphocytes B des protéines A.beta.. L'invention concerne également la vaccination à base d'acide nucléique contre des polypeptides amyloïdogènes et la vaccination à base de vaccins vivants ainsi que des procédés permettant l'identification d'analogues immunogènes utiles des protéines amyloïdogènes, des procédés permettant de préparer des analogues et des formulations pharmaceutiques, ainsi que des fragments d'acide nucléique, des vecteurs, des cellules transformées, des polypeptides et des formulations pharmaceutiques.

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