521 results about "Amyloid beta" patented technology

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.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β1-42.

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 capable of binding to amyloid-beta (Aβ) or on dialysis of blood or plasma exchange in order to remove Aβ peptides from the blood circulation, and / or brain or other affected organs.

AβN3pE-42 is a β amyloid protein that accumulates specifically as a major constituent of senile plaque in the brains of both sporadic and familial Alzheimer's disease patients. The invention provides antibodies that specifically recognize AβN3pE-42 and can be expected to have a strong β amyloid-removing action. Particularly, humanized antibodies against AβN3pE-42 are useful to treat human neurodegenerative diseases. Further, since AβN3pE-42 is localized in the brain, the antibodies of the invention can avoid side effects such as kidney disorders caused by the formation of antigen-antibody complex in the blood. An agent for gene therapy using a vector in which a cDNA encoding a protein comprises the antigen-binding region of the antibody can be an efficient therapeutic drug for removing β amyloid from the brain.

The present invention provides peptide analogs and peptide mimetics that inhibit pleated sheet formation in amyloid beta-peptide, pharmaceutical compositions thereof and their therapeutic use. The inhibitory peptides possess activity as inhibitors in the formation of amyloid-like deposits and are useful in the treatment of Alzheimer's Disease.

It is intended to provide an antibody efficacious in diagnosing, preventing or treating Alzheimer's disease, DNA encoding the antibody, a method of screening a drug and drugs. The amino acid sequence and the gene sequence of the variable region of an antibody, which specifically recognizes a GM1 ganglioside-bound amyloid β-protein occurring in the early stage of β-amyloid fibril formation, are determined. Based on the data of the amino acid sequence and the gene sequence thus obtained, an antibody is designed.

A compound of the formula:wherein Ar is an aromatic ring assembly group which may be substituted or a fused aromatic group which may be substituted; X is (i) a bond, (ii) -S-, -SO- or -SO2-, (iii) C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene, etc., (iv) -CO-O- or (v) -(CH2)p-X1-, -(CH2)p-X1- (CH2)q-, -(CH2)r-CO-X1-, -SO2-NR8- or -(CH2)r-SO2-NR8- wherein X1 is O or NR8, R8 is H, a hydrocarbon group which may be substituted or an acyl, p is 0 to 5, q is 1 to 5, p+q is 1 to 5, and r is 1 to 4; Y is a divalent C1-6 aliphatic hydrocarbon group optionally containing O or S, which may be substituted; R1 and R2 each is H or a lower alkyl which may be substituted, or R1 and R2 form a N-containing heterocyclic ring which may be substituted; Ring A is a benzene ring which may be further substituted; and Ring B is a 4- to 8-membered ring which may be further substituted, or a salt thereof has the effect of inhibiting amyloid-beta protein production and / or secretion and is useful as a pharmaceutical composition for preventing and / or treating the neurodegenerative disease, etc.

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and Aβ peptide associated diseases are also described.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.

Compositions for treating neurodegenerative or amyloidgenic disorders such as Alzheimer's disease (AD) are provided. More particularly, humanized anti-amyloid-beta antibodies, compositions containing such antibodies, corresponding nucleic acids, vectors and host cells, and methods of making such antibodies are provided.

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-,L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and / or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

The invention herein comprises antibodies that bind to amyloid beta-derived diffusible ligands (ADDLs). ADDLs comprise amyloid β protein assembled into soluble, globular, non-fibrillar, oligomeric structures capable of activating specific cellular processes.

The invention pertains to the development of antibodies that specifically bind amyloid beta protein (Abeta) in its protofibril conformation. The invention also comprises methods of using anti-Abeta protofibril antibodies to diagnose or treat Alzheimer's disease, Down's syndrome Lewybody dementia, vascular dementia, and other neurodegenerative disorders. Furthermore, the invention pertains to the use of anti-Abeta protofibril antibodies to screen and identify substances that will modulate protofibril activity or formation in vitro or in vivo. The invention also pertains to methods for synthesising pure Abeta protofibril antigens as well as to a method for stabilising Abeta protofibrils antigens as well as to a method for stabilising Abeta protofibrils.

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (a) and include tautomers, solvates, prodrugs, esters, and deuterates thereof, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, ring C, m, n, p, q, -L1-, -L2-, L3-, and L4- is selected independently and as defined herein. The compounds of the invention have, surprisingly and advantageously, improved solution stability. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

The present invention provides compounds having the formula:wherein R1, R′, R2, R3, R3′, R4, X1, X2 and X3 are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer's Disease). The present invention also provides methods for preparing compounds of the invention.

This invention describes the administration of multiple therapeutic agents with insulin in conjunction with bexarotene, ketamine, monoclonal antibodies Etanercept, IGF-1, and acetylcholine esterase inhibitors physostigmine, for treatment of Alzheimer's disease and other neurodegenerative diseases. Insulin, improves memory; also augments and amplifies the effects of the adjuvant therapeutic agents (paracrine and intracrine effects) and consequently reduces the β amyloid, its soluble precursors, prevents damage to the neuronal skeletal network (taupathy), and blocks glutamate excitotoxicity, reduces brain inflammation, prevents apoptosis, and increases the acetylcholine levels in the neurons and synapses; by using a combination of insulin, bexarotene, ketamine, Etanercept, IGF-1, and physostigmine therapeutic agents. The results are achieved by using the specially designed Iontophoresis incorporated olfactory mucosal delivery (ORE) catheter device located at the olfactory nerves, sphenoid sinus, and adjacent structures described here, to transport the large molecules of therapeutic agents to treat AD delivered to the CNS bypassing BBB from ORE.

Disclosed herein is a method for prophylaxis or treatment of a neurodegenerative disease associated with aggregation of amyloid-beta (Aβ) in a subject. The method includes the step of, administering to the subject an effective amount of a compound having formula (I),wherein, R1 is selected from the group consisting of —SC3H6OH, —SC2H4COOH, —SCH2CHOHCH3, —SCH2CHOHCH2OH, —S(C6H4)OH, —SC2H4OH, —OH, and —NHC2H4(NC2H4OC2H4); and R2 is H or CH3.

The present invention pertains to novel diagnostic assays for the diagnosis of amyloidosis, in particular Alzheimer's disease, and related aspects. In particular, monoclonal antibodies and an antibody assay are provided.

Antibodies directed to the C-terminal side of β-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described.

The present invention relates to compositions and methods for the treatment of neurological disorders related to glutamate excitotoxicity and Amyloid β toxicity. More specifically, the present invention relates to novel combinatorial therapies of Multiple Sclerosis, Alzheimer's disease, Alzheimer's disease related disorders, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, neuropathic pain, alcoholic neuropathy, alcoholism or alcohol withdrawal, or spinal cord injury.

The present invention relates to immunogenic but non-depositing-forming polypeptides or peptides homologous to amyloid β, prion, amylin or α-synuclein which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid β peptides and amyloid deposits, to prion protein and prion deposits, to amylin and amylin deposits, to α-synuclein and deposits containing α-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.

Compositions and methods for identifying modulators of sortilin are described. The methods are particularly useful for identifying analytes that antagonize sortilin s effect on processing of amyloid precursor protein to Aβ peptide and thus useful for identifying analytes that can be used for treating Alzheimer disease.

The invention described in this disclosure involves a new composition of matter, amyloid beta-derived dementing ligands (ADDL's). ADDLs consist of amyloid β peptide assembled into soluble globular non-fibrillar oligomeric structures that are capable of activating specific cellular processes. The invention further encompasses methods for assaying the formation, presence, receptor protein binding and cellular activities of ADDLs. The invention further encompasses assay methods and inhibitor molecules for cellular signaling molecules activated by ADDLs. Also described are molecules that block proteins that promote the formation of ADDLs.

The present invention is intended to devise a process of measuring β-amyloid in a biological sample such as blood and to apply the process to diagnosis of Alzheimer's disease.It is possible to assay Alzheimer's disease by measuring a total amount of β-amyloid 1-42 and β-amyloid 1-42 fragments each of which retains a C-terminal site of the β-amyloid 1-42 in the biological sample by an immunological assay in which an antibody which recognizes the C-terminal site of β-amyloid 1-42 is used. It is preferable that the immunological assay be a competitive immunological assay.

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.

This invention relates to antibodies, including specified portions or variants, specific for at least the human Amyloid-beta 11 N-terminal site, i.e. Aβ11-x peptides. It further provides methods of making and using said antibodies, including therapeutic formulations, administration and devices.

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing CNS and amyloid associated disease. Also described are methods, compounds, pharmaceutical compositions and kits for detecting, diagnosing, monitoring and treating or preventing CNS and amyloid associated disease.

A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble Aβ peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ.