New York University

Other

Blas Frangione

Thomas M Wisniewski

Einar M Sigurdsson

Jorge Ghiso

Marc Henrik Baumann

Claudio Soto-Jara

Miguel A Pappolla

Jose Alejandro Chabalgoity

Fernando Goni

Fernando R Goni

Marcin Sadowski

Ruben Vidal

Burkhard Poeggeler

Vaccines against prion disease eliciting a humoral immune response when administered mucosally are described. The vaccines comprise a prion protein, a prion protein fragment, or a non-amyloidogenic prion protein homolog and an adjuvant suitable for inducing a humoral immune response after mucosal administration. Suitable adjuvants include cholera toxin subunit B, heat-labile enterotoxin and aluminum hydroxide. Alternatively, the vaccine comprises a vector encoding a prion protein, fragment, or homolog in an attenuatedhost. The vaccines can be used to prevent or treat prion disease in humans and other mammals.

Mucosal immunization to prevent prion infection

Disclosed herein are methods for treating amyloid disease in humans by clearing amyloid peptides from one or more bodily fluids such as, e.g., blood, of a patient. In particular, the methods are based on the administration of compounds capable of binding to amyloid-beta (A&#x3b2;) or on dialysis of blood or plasma exchange in order to remove A&#x3b2; peptides from the blood circulation, and/or brain or other affected organs.

Method for treating amyloid disease

Disclosed herein are methods for treating amyloid disease in humans by clearing amyloid peptides from one or more bodily fluids such as, e.g. blood, of a patient. In particular, the methods are based on the administration of compounds capable of binding to amyloid-beta (A&#x3b2;) or on dialysis of blood or plasma exchange in order to remove A&#x3b2; peptides from the blood circulation, and/or brain or other affected organs.

The present invention relates to synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid &#x3b2; which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid &#x3b2; peptides and amyloid deposits.

Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid &#x3b2; for induction of an immune response to amyloid &#x3b2; and amyloid deposits

The present invention is directed to a method of preventing or treating Alzheimer's Disease or of inhibiting accumulation of amyloid-&#x3b2; deposits in a subject by administering to the subject an agent which inhibits interaction between amyloid-&#x3b2; and proteins which chaperone amyloid-&#x3b2; under conditions effective to prevent or treat Alzheimer's Disease in the subject or to inhibit accumulation of amyloid-&#x3b2; deposits in the subject's brain, respectively. Another embodiment of the present invention relates to a method of inhibiting interaction between apolipoprotein E and amyloid-&#x3b2; by administering an agent which blocks interaction of apolipoprotein E and amyloid-&#x3b2; under conditions effect to block such interaction.

Treatment of Alzheimer amyloid deposition

The present invention relates to immunogenic but non-depositing-forming polypeptides or peptides homologous to amyloid &#x3b2;, prion, amylin or &#x3b1;-synuclein which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid &#x3b2; peptides and amyloid deposits, to prion protein and prion deposits, to amylin and amylin deposits, to &#x3b1;-synuclein and deposits containing &#x3b1;-synuclein, or to polyglutamine repeats and deposits of proteins containing polyglutamine repeats. Described are also antibodies directed against such peptides, their generation, and their use in methods of passive immunization to such peptides and deposits.

Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid &#x3b2;, prion protein, amylin, &#x3b1;-synuclein, or polyglutamine repeats for induction of an immune response thereto

Synthetic immunogenic but non amyloidogenic peptides homologous to amyloid &#x3b2;  for induction of an immune response to amyloid &#x3b2;  and amyloid deposits

The present invention relates to synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid &bgr; which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid &bgr; peptides and amyloid deposits.

Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid &bgr; for induction of an immune response to amyloid &bgr; and amyloid deposits

Two novel mutant amyloid protein precursors (ABriPP and ADanPP) and their amyloid peptides (ABri and ADan) associated with Familial British Dementia and Familial Danish Dementia, respectively, are disclosed. Genetic constructs comprising DNA encoding these proteins is used to produced transgenic mammals that are useful models for neurological diseases associated with amyloid deposits, neurofibrillary tangles, non-neuritic plaques, neuronal degeneration and behavioral deficits characteristic of dementia and other symptoms of the human diseases. These models are used for testing potential therapeutic agents and methods. Also provided is a DNA-based test for detecting the mutations, the mutant proteins and peptides, antibodies specific for the proteins and peptides. Immunoassays permit detection of the mutant proteins, particularly in affected brain tissue, or detection of an antibody specific for a mutant peptide.

Mutant genes in Familial British Dementia and Familial Danish Dementia

Novel peptides capable of interacting with a hydrophobic &bgr;-sheet forming cluster of amino acid residues on a protein or peptide for amyloid or amyloid-like deposit formation inhibit and structurally block the abnormal folding of proteins and peptides into amyloid or amyloid-like deposits and into pathological &bgr;-sheet-rich conformation as precursors thereof. Methods for preventing, treating or detecting disorders or diseases associated with amyloid-like fibril deposits, such as Alzheimer's disease and prion-related encephalopathies, are also provided.

Peptides and pharmaceutical compositions thereof for treatment of disorders or diseases associated with abnormal protein folding into amyloid or amyloid-like deposits

The cytotoxic effects of amyloid beta protein on cells are prevented by contacting the cells with an effective amount of an indole-3-propionic acid or a salt or ester thereof. Furthermore, a fibrillogenic disease can be treated in a human subject by administering to the human subject an amount of-an indole-3-propionic acid or a salt or ester thereof effective to prevent or reverse fibrillogenesis. Oxidation in a biological sample can be decreased by contacting the biological sample with an effective amount of an indole-3-propionic acid or a salt or ester thereof. Additionally, diseases or other conditions where free radicals and/or oxidative stress play a role can be treated by administering an effective amount of an indole-3-propionic acid or a salt or ester thereof.

Uses for indole-3-propionic acids and salts and esters thereof

The present invention relates to a method of using melatonin to reduce, inhibit or reverse the formation of amyloid fibrils and amyloid or amyloid-like deposits. The present invention also relates to a method for delaying the onset of Alzheimer's Disease or other amyloidosis-related diseases/disorders or for treating such diseases/disorders by administering an effective amount of melatonin to a subject in need thereof.

Method for delaying the onset of alheimer's disease and for treatment or delaying the onset of other amyloidosis-related diseases/disorders

Novel peptides capable of interacting with a hydrophobic structural determinant on a protein or peptide for amyloid or amyloid-like deposit formation inhibit and structurally block the abnormal folding of proteins and peptides into amyloid or amyloid-like deposits. Methods for preventing, treating or detecting disorders or diseases associated with amyloid-like fibril deposits, such as Alzheimer's disease and prion-related encephalopathies, are also provided.

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New York, NY, United States of America

Blas Frangione