161 results about "Amyloid β peptide" patented technology

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

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

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

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.

Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and / or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.

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

A unique DHA product, 10, 17S-docosatriene (“Neuroprotectin D1” or “NPD1”), was found to provide surprisingly effective neuroprotection when administered right after an experimental stroke. Moreover, both nerve cells and retinal pigment epithelial (RPE) cells were found to synthesize 10,17S-docosatriene (NPD1) from DHA. NPD1 also potently counteracted H2O2 / TNFα oxidative stress-mediated cell apoptotic damage. Under the same oxidative-stress conditions, NPD1 up-regulated the anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-xL, and decreased expression of the pro-apoptotic proteins, Bad and Bax. Moreover, in RPE cells NPD1 inhibited oxidative stress-induced caspase-3 activation, IL-1β-stimulated human COX-2 promoter expression, and apoptosis due to N-retinylidene-N-retinylethanolamine (A2E). Overall, NPD1 protected both nerve and retinal pigment epithelial cells from cellular apoptosis and damage due to oxidative stress. NPD1 concentration in the brain of Alzheimer's patients was found to be significantly decreased from that of controls. In cultured human brain cells, NPD1 synthesis was up-regulated by neuroprotective soluble β amyloid, and NPD1 was found to inhibit secretion of toxic β amyloid peptides.

There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I)wherein R, R1, R2 and R3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

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

There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I) wherein R, R1, R2 and R3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

The invention relates to a method for the in vitro diagnosis of Alzheimer's disease using a monoclonal antibody. Said antibody can bind at least to amino acids 12-16 of the β-amyloid peptide, specifically detecting the neuritic plaques which are characteristic of Alzheimer's disease, without detecting diffuse plaques which are not defining characteristics of the disease. Within the neuritic plaques, the monoclonal antibody can detect a different sub-group in the composition of the different deposited isoforms of the β-amyloid peptide, which is associated with the disease progression stage. In addition, the antibody can bind to isoforms of the β-amyloid peptide in biological fluids such as urine. As a result, the inventive monoclonal antibody, the cell lines that produce said antibody and compositions containing same can be used in the in vitro diagnosis of Alzheimer's disease and in determining the disease progression stage.

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 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.

The present disclosure provides a series of compounds of the formula (I)which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.

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.

2-arylbenzothiophene derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition for the diagnosis or treatment of degenerative brain disease containing the same as an active ingredient. Since the 2-arylbenzothiophene derivatives of Formula 1 have a relatively high binding affinity for β-amyloid, they can be used as diagnostic reagents for diagnosing Alzheimer's disease at an early stage by non-invasive techniques when they are labeled with radioisotopes:wherein R1-R4, V, W, X, Y and Z are as defined in the Detailed Descript of the specification. Further, when the pharmaceutical composition containing the 2-arylbenzothiophene derivative binds with a low-molecular weight β-amyloid peptide binding compound, generation of malignant high-molecular weight β-amyloid deposits is minimized. Accordingly, the pharmaceutical composition can be used as a therapeutic agent of degenerative brain disease such as Alzheimer's disease.

The present invention relates to a composition comprsing a peptide immunogen useful for the prevention and treatment of Alzheimer's Disease. More particularly, the peptide immunogen comprises a main functional / regulatory site, an N-terminal fragment of Amyloid β (Aβ) peptide linked to a helper T cell epitope (Th) having multiple class II MHC binding motifs. The peptide immunogen elicit a site-directed immune response against the main functional / regulatory site of the Aβ peptide and generate antibodies, which are highly cross-reactive to the soluble Aβ1-42 peptide and the amyloid plaques formed in the brain of Alzheimer's Disease patients. The antibodies elicited being cross reactive to the soluble Aβ1-42 peptide, promote fibril disaggregation and inhibit fibrillar aggregation leading to immunoneutralization of the “soluble Aβ-derived toxins”; and being cross-reactive to the amyloid plaques, accelerate the clearance of these plaques from the brain. Thus, the composition of the invention comprising the peptide immunogen is useful for the prevention and treatment of Alzheimer's Disease.

This invention is directed to a class of compounds (Formula I) including succinoyl amino pyrazoles, succinoyl amino thiadiazoles, succinoyl amino acid esters, succinoyl amino acid amides, succinoyl amino alcohols, succinoyl amino ketones, succinoyl amino hydantoins, succinoyl anilines, and succinoyl derivatives of privileged structures. The invention is also directed to a pharmaceutical formation comprising such compound in a pharmaceutically acceptable salt form or prodrug thereof. The invention is further directed to a method for inhibiting β-amyloid peptide release and / or synthesis, a method for inhibiting γ-secretase activity and a method for treating neurological disorders associated with β-amyloid peptide production. The method comprises administering to a host a pharmaceutical formulation comprising an effective amount of a compound of Formula I. The compounds of Formula I are useful in the prevention and treatment of Alzheimer's disease.

A human anti-amyloid β peptide (hereinafter referred to as “Aβ”) antibody that binds to Aβ to thereby inhibit aggregation of Aβ molecules, and a fragment of said antibody are provided. The antibody and a fragment thereof according to the present invention, comprising a variable region of a human-derived anti-Aβ antibody, strongly reacts with Aβ to thereby inhibit its aggregation and hence may be used as a medicament for the prophylaxis and treatment of Alzheimer dementia.

The present invention relates to an amyloid β peptide analogues comprising an amino acid sequence or a peptidomimetic thereof, wherein the sequence (i) forms a loop, (ii) has at least 66% identity to the amino acid sequence of native Aβ peptide or a portion thereof, (iii) comprises at least 6 contiguous amino acid residues and (iv) has at least 2 non-contiguous amino acid residues which are covalently linked with each other, oligomers comprising a plurality of said amyloid β peptide analogues, processes for preparing the amyloid β peptide analogues or oligomers, compositions comprising the amyloid β peptide analogues or oligomers, and uses of the amyloid β peptide analogues or oligomers such as their use for treating or preventing an amyloidosis (e.g. by active immunization), for diagnosing an amyloidosis, and for providing agents that are capable of binding to the amyloid β peptide analogues or oligomers. The subject invention also describes agents that are capable of binding to the amyloid β peptide analogues or oligomers, e.g. antibodies, compositions comprising the agents, and uses of the agents such as their use for treating or preventing an amyloidosis (e.g. by passive immunization) and for diagnosing an amyloidosis.

The present invention relates to methods for screening, identifying, and / or quantifying modulators of amyloid and / or aggregates, fibrils or components thereof, in particular modulators of amyloid β-peptide (Aβ) or Aβ fibrils. Aspects of the invention provide methods for screening putative modulators against an Amyloid target, in particular an Aβ target, so as to determine which modulators bind to or interact with the target, or interfere with the interaction of an indicator agent and the target. Particular aspects of the invention employ mass spectrometric methods for the screening of an Amyloid target against compound libraries, in particular mixtures of compounds or combinatorial libraries.

The present invention relates to methods and compositions for modulating levels of amyloid-β peptide (Aβ) exhibited by non-neuronal (i.e., peripheral) cells, fluids, or tissues. The invention also relates to modulation of Aβ levels via selective modulation (e.g., inhibition) of γ-secretase activity. The invention also relates to methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an Aβ-related disorder, by administering a compound that result in the modulation of γ-secretase in a non-neuronal tissue, either directly or indirectly to prevent, treat or ameliorate the symptoms of a brain Aβ disorder, such as Alzheimer's disease.

Antibodies that bind human β-amyloid peptide, methods of treating diseases or disorders characterised by elevated β-amyloid levels or β-amyloid deposits with said antibodies, pharmaceutical compositions comprising said antibodies and methods of manufacture.

The invention concerns a peptide having the biological activity of an inhibitor of amyloid formation and its diagnostic and medical use.

The invention relates to methods of treating a subject having Alzheimer's Disease, comprising the step of administering an antibody molecule which is targeted to β amyloid peptide or to fragment thereof. In another embodiment the invention relates to methods of treating a disease or a disorder, characterized by amyloid beta deposition. In another embodiment, the invention relates to an antibody molecule, which is free end-specific for the N-terminus or the C-terminus of an amyloid β peptide and to a pharmaceutical composition thereof. In another embodiment, the invention relates to an antibody molecule, which is targeted to the free C or N-terminus of a N-and / or C-terminus truncated amyloid β peptide fragment.

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in 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, predicted mutations in the APP gene, and truncated forms of APP that contain the Aβ region. 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 of APP, β-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

The subject invention concerns the reduction of protein aggregation in the neurons of a mammal through the use of a ketogenic treatment such as a ketogenic diet, a physical training regimen and / or administration of agents to increase fatty acid oxidation. Such ketogenic treatment can be useful in the reduction of certain aggregates including amyloid β peptide, polyglutamine containing huntintin protein, polyglutamine containing androgen receptor, polyglutamine containing atrophin-1, polyglutamine containing ataxins, α-synclein, prion protein, tau and superoxide dismutase 1 (SOD1).