The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Albumin Fusion Proteins

The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is Aβ peptide or an antibody thereto.

Prevention and treatment of amyloidogenic disease

The invention provides improves agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Preferred agents include humanized antibodies.

Humanized antibodies that recognize beta amyloid peptide

Novel compounds, compositions, and kits are provided. Methods of modulating Aβ levels, and methods of treating a disease associated with aberrant Aβ levels are also provided.

Compounds and uses thereof in modulating amyloid beta

The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.

Transgenic animals harboring app allele having swedish mutation

The construction of transgenic animal models for testing potential treatments for Alzheimer's disease are described. The models are characterized by a greater similarity to the conditions existing in naturally occurring Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP 695 , APP 751 , and APP 770 ), as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, and predicted mutations in the APP gene. The APP gene constructs are prepared using the naturally occurring promoter, as well as inducible promoters such as the mouse metallothionine promoter, which can be regulated by addition of heavy metals such as zinc to the animal's water or diet, and promoters such as the rat neuron specific enolase promoter, human β actin gene promoter, human platelet derived growth factor B (PDGF-B) chain gene promoter, rat sodium channel gene promoter, mouse myelin basic protein gene promoter, human copper-zinc superoxide dismutase gene promoter, and mammalian POU-domain regulatory gene promoter. The constructs are introduced into animal embryos using standard techniques such as microinjection. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's Disease as measured by their effect on the amount and histopathology of APP and β-amyloid peptide in the animals, as well as by behavioral alterations.

Transgenic mouse assay for compounds affecting amyloid protein processing

The construction of transgenic animal models for testing potential treatments for Alzheimer's disease are described. The models are characterized by a greater similarity to the conditions existing in naturally occurring Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, and predicted mutations in the APP gene. The APP gene constructs are prepared using the naturally occurring promoter, as well as inducible promoters such as the mouse metallothionine promoter, which can be regulated by addition of heavy metals such as zinc to the animal's water or diet, and promoters such as the rat neuron specific enolase promoter, human β actin gene promoter, human platelet derived growth factor B (PDGF-B) chain gene promoter, rat sodium channel gene promoter, mouse myelin basic protein gene promoter, human copper-zinc superoxide dismutase gene promoter, and mammalian POU-domain regulatory gene promoter. The constructs are introduced into animal embryos using standard techniques such as microinjection. Animal cells can be isolated from the transgenic animals or prepared using the same contructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount and histopathology of APP and β-amyloid peptide in the animals, as well as by behavioral alterations.

Transgenic animal models for alzheimer's disease

The construction of transgenic mouse models for testing potential treatments for Alzheimer's disease are described. The models are characterized by a greater similarity to the conditions existing in naturally occurring Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP 695 , APP 751 , and APP 770 ), as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, and predicted mutations in the APP gene. The APP gene constructs are prepared using the naturally occurring promoter, as well as inducible promoters such as the mouse metallothionine promoter, which can be regulated by addition of heavy metals such as zinc to the mouse's water or diet, and promoters such as the rat neuron specific enolase promoter, human β actin gene promoter, human platelet derived growth factor B (PDGF-B) chain gene promoter, rat sodium channel gene promoter, mouse myelin basic protein gene promoter, human copper-zinc superoxide dismutase gene promoter, and mammalian POU-domain regulatory gene promoter. The constructs are introduced into mouse embryos using standard techniques such as microinjection. Mouse cells can be isolated from the transgenic mice or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic mice, or mouse cells, are used to screen for compounds altering the pathological course of Alzheimer's Disease as measured by their effect on the amount and histopathology of APP and β-amyloid peptide in the mice, as well as by behavioral alterations.

Transgenic mouse expressing APP770

A nucleic acid construct is described which when expressed in cells, results in the production of APP695, APP751 and APP770. The construct is the cDNA for APP770 with the genomic sequences encoding the KI and OX-2 regions substituting for those regions present in the cDNA.

cDNA-genomic DNA hybrid sequence encoding APP770 containing a genomic DNA insert of the KI and OX-2 regions

Cette invention concerne la construction de modeles d'animaux transgeniques utilises pour tester des traitements potentiels de la maladie d'Alzheimer. Ces modeles se caracterisent par leur plus grande similarite aux troubles lies a la maladie d'Alzheimer apparaissant naturellement, qui se fondent sur l'expression des trois formes de la proteine de precurseur β-amyloide (APP) , APP695, APP751 et APP770, ainsi que sur diverses mutations ponctuelles basees sur des mutations d'origine naturelle telles que les mutations de maladie d'Alzheimer familiale de Londres et d'Indiana au niveau de l'acide amine 717, et des mutations prevues dans le gene APP. On prepare les structures de gene APP en utilisant le promoteur d'origine naturelle ainsi que des promoteurs pouvant etre induits tels que le promoteur de metallothionine de souris qui peut etre regule par addition de metaux lourds tels que du zinc, dans le regime alimentaire ou l'eau de l'animal, et des promoteurs tels que le promoteur d'enolase specifique des neurones du rat, le promoteur du gene d'actine β humain, le promoteur du gene de la chaine du facteur B de croissance derive des plaquettes humaines (PDGF-B), le promoteur du gene de canal de sodium du rat, le promoteur du gene de proteine basique de myeline de souris, le promoteur du gene de superoxyde-dismutase cuivre-zinc humain, et le promoteur du gene regulateur du domaine POU de mammifere. Ces structures sont introduites dans des embryons d'animaux au moyen de techniques classiques telles que la micro-injection. Des cellules d'animaux peuvent etre isolees des animaux transgeniques ou preparees a l'aide de ces memes structures par des techniques classiques telles que la lipofection ou l'electroporation. Les animaux transgeniques, ou les cellules d'animaux transgeniques sont utilises pour tester les composes modifiant l'evolution pathologique de la maladie d'Alzheimer, dont on mesure les effets sur la quantite et l'histopathologie de l'APP et du peptide β-amyloide chez les animaux, ainsi que sur les modifications du comportement.

Benjamin Snyder

Papers

Transgenic mouse assay for compounds affecting amyloid protein processing

Transgenic animal models for alzheimer's disease

Transgenic mouse expressing APP770

cDNA-genomic DNA hybrid sequence encoding APP770 containing a genomic DNA insert of the KI and OX-2 regions

Modeles d'animaux transgeniques utilises pour tester des traitements potentiels relatifs a la maladie d'alzheimer