66 results about "Aβ oligomers" patented technology

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

In various aspects, the present invention provides methods and kits for predicting the therapeutic efficacy of an immunological reagent, identifying an immunological reagent having therapeutic efficacy, or both, for the treatment of an amyloidogenic disorder by comparing the amount of Aβ monomer in an Aβ preparation which binds to the immunological reagent to an amount of one or more Aβ oligomers in the Aβ preparation which bind to the immunological reagent to determine a relative bound amount, and predicting the efficacy of the immunological reagent, identifying an immunological reagent having therapeutic efficacy, or both, for the treatment of an amyloidogenic disorder based at least on the relative bound amount.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble A beta oligomers, but do not recognize soluble A beta monomers, which are physiological molecules. It was demonstrated that the anti-bodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The invention relates to a nucleic acid aptamer electrochemical sensor based on metal organic framework materials (MOFs) as signal probes. The senor is used for detection of beta-amyloid (A beta) oligomers and belongs to the technical field of functional nanocomposite materials and biosensor detection. AuNFs-modified glassy carbon electrodes immobilize a first layer of aptamers, the A beta oligomer is further identified and through combination with second layer aptamer-modified gold nanoparticle-loaded Cu-MOFs (AuNPs / Cu-MOFs), the sandwich electrochemical sensor for detection of the A beta oligomer is formed. AuNPs / Cu-MOFs as a redox medium can directly detect a Cu<2+> signal and electrochemically active molecule labeling is avoided so that the detection processes are greatly simplified and the sensitivity of detection is improved.

The invention relates to a method for the preparation of a stable, soluble amyloid beta (Aβ) oligomer and composition thereof for use as an antigen for the generation of antibodies for the treatment of Alzheimer's disease and other conditions related to abnormal amyloid beta aggregation. The method which uses a pH in excess of 7.0 and high concentrations of Aβ, optionally includes the use of divalent anions or a helix-inducing solvent to form the oligomers. The stable, soluble Aβ oligomers produced by the method herein have a particle size of 10 to 100 nm in diameter, when measured by a dynamic light scattering technique, and a molecular weight of 100 to 500 kDa.

Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and / or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane / lipid raft (CM / LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i)

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The invention provides an anti-Alzheimer disease monoclonal antibody which can specifically identify and combine Abeta oligomers and can be used in the preparation of diagnostic reagents and treatment drugs for Alzheimer disease.

The invention herein is directed to a selective Aβ oligomer immunoassay capable of reliably and sensitively detecting Aβ oligomers in a biological sample of a patient. In one embodiment the inventive assay uses a pair of anti-AP oligomer antibodies, 19.3 and 82E1, to detect and quantify Aβ oligomers in a cerebrospinal fluid (CSF) sample. The inventive assay can be used to differentiate Alzheimer's disease (AD) patients from non-AD patients and / or to stratify AD patients according to the severity of their disease. The inventive assay can also be used as a target engagement assay that can measure bound Aβ oligomers as a surrogate end-point for the assessment of therapeutic efficacy and / or target engagement.

The invention discloses novel medical application of Alpha-mangostin, i.e. application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease. Under a brand-new working concentration, the Alpha-mangostin shows the characteristic of restricting A Beta accumulation and deposition, simultaneously has a neuroprotection role, can effectively resist a neurotoxin role caused by A Beta oligomer, strengthen the normal physiological function of neuron cells of mammals and maintain the normal cell form of the neuron cells of the mammals, realizes the intervention to the pathological course of the Alzheimer's disease and the improvement to the pathological symptoms and provides a new path for treatment of the Alzheimer's disease.

A peptide probe that generates fluorescence signals rapidly upon recognition of various Aβ aggregates without significant perturbation of samples. The present peptide probes display an increase in fluorescence signals upon coincubation with Aβ oligomers, but neither monomeric / dimeric species nor fibrils. The detection can occur within an hour or two without any additional sample preparation and incubation steps.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble A beta oligomers, but do not recognize soluble A beta monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The invention relates to binding molecules capable of specifically recognizing soluble oligomers of N-terminal truncated Aβ starting with pyroglutamate (AβρE), pharmaceutical compositions comprising same, and their respective therapeutic uses. Particularly, the invention relates to an antibody molecule capable of specifically recognizing Aβ oligomers, wherein said antibody binds and / or detects an epitope as bound and / or detected by antibody PG3-38 9D5H6 as deposited under DSM AC-C3056. Further, the invention provides a method of inhibiting the formation or the seeding effect of said AβρE oligomers, and a method for identifying agents useful in the treatment and / or prevention of an amyloid-related disorder as well as methods of diagnosing a subject suspected of suffering from a disease associated with amyloidogenesis and / or amyloid plaque formation and to methods of monitoring the efficacy of a treatment of a disease associated with amyloidogenesis and / or amyloid-plaque formation characterized by the presence of Aβ oligomers in a subject.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The present invention provides compositions and methods for treating and preventing an Aβ-modulated disease. In certain embodiments, the invention provides an inhibitor of Fyn tyrosine kinase, and methods of using the same. In certain embodiments, the inhibitor of the invention inhibits Aβ oligomer induced signaling and reduces or halts the progression of Alzheimer's Disease.

This invention is a selective Aβ oligomer kit and immunoassay method capable of reliably and sensitively detecting Aβ oligomers in a biological sample of a patient. In one embodiment the inventive assay uses a pair of anti-Aβ oligomer antibodies, as capture and detection antibodies, to detect and quantify Aβ oligomers. The method can be used to differentiate Alzheimer's disease (AD) patients from non-AD patients and / or to stratify AD patients according to the severity of their disease.

An anti-cognitive dysfunction agent comprising a humanized antibody which does not bind to Aβ monomers and specifically binds only to Aβ oligomers and a fragment thereof as an active ingredient, and an therapeutic antibody which can be treat Alzheimer's disease by specifically binding amyloid β protein oligomer (Aβ oligomer) which is considered to be a cause of Alzheimer's disease are required. The present invention can provide an anti-Aβ oligomer humanized antibody and a method for treating Alzheimer's disease using the humanized antibody. An agent for treating Alzheimer's disease; an agent for suppressing formation of neuritic plaque; an inhibitor of formation of Aβ amyloid fiber; a method for at least one of preventing and treating cognitive dysfunction or Alzheimer's disease, comprising the step of administering the humanized antibody; and a method for suppressing progression of Alzheimer's disease, comprising the step of administering the humanized antibody.

The invention relates to binding molecules capable of specifically recognizing soluble oligomers of N-terminal truncated Aβ starting with pyroglutamate (AβρE), pharmaceutical compositions comprising same, and their respective therapeutic uses. Particularly, the invention relates to an antibody molecule capable of specifically recognizing Aβ oligomers, wherein said antibody binds and / or detects an epitope as bound and / or detected by antibody PG3-38 9D5H6 as deposited under DSM AC-C3056. Further, the invention provides a method of inhibiting the formation or the seeding effect of said AβρE oligomers, and a method for identifying agents useful in the treatment and / or prevention of an amyloid-related disorder as well as methods of diagnosing a subject suspected of suffering from a disease associated with amyloidogenesis and / or amyloid plaque formation and to methods of monitoring the efficacy of a treatment of a disease associated with amyloidogenesis and / or amyloid-plaque formation characterized by the presence of Aβ oligomers in a subject.

An anti-Aβ oligomer humanized antibody which does not bind to Aβ monomers and specifically binds only to Aβ oligomers; an anti-cognitive dysfunction agent, an agent for treating Alzheimer's disease, an agent for suppressing formation of neuritic plaque and an inhibitor of formation of Aβ amyloid fiber comprising the antibody as an active ingredient; a method for at least one of preventing and treating cognitive dysfunction or Alzheimer's disease, comprising the step of administering the antibody; and a method for suppressing progression of Alzheimer's disease, comprising the step of administering the antibody.

Agents for treating Alzheimer's disease comprising a peptide according to sequence no. 1 which binds to Aβ oligomers and thus results in the healing or alleviation of Alzheimer's disease. In further embodiments peptides are provided which contain a sequence no. 1, but have preceding sequence sections which allow the peptide to be secreted. For the purpose of gene therapy, corresponding DNA sequences and vectors, in particular according to sequences 3 to 6, are provided.

The invention discloses a preparation process for an A beta oligomer antibody. The preparation process comprises the following steps that the conductivity, the pH and the protein concentration of an upper chromatographic column front sample are adjusted; affinity gel chromatography is conducted; eluent from an affinity chromatographic column is filtered, ultra-filtered and prepared; and virus inactivation and sterilized sub-packaging are conducted. According to the preparation process for the A beta oligomer antibody, one-step affinity chromatography is adopted, the purification multiple is 85-100 times, and the A beta oligomer antibody obtained through purification is high in concentration and clear in targeting performance and has wide clinical application prospects.

The present invention provides a method for screening a therapeutic and / or prophylactic agent for Alzheimer's disease using at least one index selected from the group consisting of the levels of Aβ oligomers, BiP, cleaved caspase 4, PRDX4 and ROS in nerve cells or the like whose differentiation has been induced from iPS cells derived from somatic cells of a patient with Alzheimer's disease.

The present invention pertains to stabilized Aβ oligomer compositions. Methods for generating stabilized Aβ oligomer compounds are also provided herein. Additionally, screening assays employing the Aβ oligomer compounds and methods for generating therapeutics with the Aβ oligomers are also provided. In a particular embodiment, the Aβ oligomer described herein is comprised of Aβ42 peptide.

Aspects of the invention relate to methods and compositions for treating Alzheimer's disease (AD). In some embodiments, the invention provides methods for screening and identifying compounds that selectively inhibit the targeting of the insulin-Akt signaling pathway by Aβ oligomers.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble A beta oligomers, but do not recognize soluble A beta monomers, which are physiological molecules. It was demonstrated that the anti-bodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The invention discloses a polypeptide used for treating alzheimer disease (AD). The amino acid sequence of the polypeptide is Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala. The polypeptide is smart in concept, an Abeta1-42 carboxyl terminal polypeptide Abeta31-42 is taken as an antigen, Th1 immune cell mediated self immunity inflammatory reactions, induced by Abeta16-30, are avoided, an organism can also be effectively induced to produce an antibody for identifying an Abeta1-42 carboxyl terminal, Abeta oligomerization is prevented, neurovirulence of an Abeta oligomer is effectively inhibited, and the aim of treating AD is achieved.

The invention discloses a method for detecting and accelerating beta-amyloid protein aggregation by means of a lanthanide fluorescence complex, and belongs to the technical field of medicines. According to the method, the lanthanide fluorescence complex is used for detecting A-beta aggregate, an imidazo[1,2,a]pyridine derivative serves as an antenna group to be coupled with a europium (III)-DTPA luminescence center to prepare a fluorescence complex Eu-L, the antenna group can be selectively combined with A-beta hydrophobic region amino acid residues with the beta-folding conformation, photoinduced electron transfer of amino acid hinders energy transfer from the antenna group to europium (III), Eu-L fluorescence is reduced, and the A-beta aggregate is detected by means of fluorescence changes. According to the method, the lanthanide fluorescence complex is further used for accelerating A-beta aggregation, on the basis of high affinity of the antenna ligand and the A-beta aggregate, the Eu-L can accelerate conversion of A-beta oligomers into corpus fibrosum, the A-beta aggregation process is simultaneously monitored by means of autofluorescence, and a good application prospect in the aspect of AD diagnosis and treatment is achieved.