182 results about "Alpha-synuclein" patented technology

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to fill-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

Disclosed are antibodies specific for alpha-synuclein conformers and methods related thereto. For example, disclosed are methods of diagnosing a neurodegenerative monitoring a neurodegenerative disease treatment using the disclosed antibodies. Assays, kits, and solid supports related to alpha-synuclein and antibodies specific for alpha-synuclein are also disclosed.

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

A vaccine for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble α-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the α-synuclein. An antibody for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual binds soluble α-synuclein. Methods for delaying an onset of for treatment or for prevention of an α-synuclein-related disorder employ the vaccine or antibody. Methods of detecting α-synuclein oligomers employ the antibody.

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

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 invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

The invention relates to translation enhancer elements that enhance translation of the gene encoding the human microtubule-associated tau protein and nucleic acid molecules that enhance translation of the gene encoding the human α-synuclein protein. The translation enhancer elements of the invention are useful in compositions and methods for identifying compounds for the prevention and / or treatment of neurodegenerative disease. The invention also includes in some aspects, vectors that include a translation enhancer element of the invention. The invention also includes the use of enhancer element containing vectors in methods to produce recombinant protein and in assays to identify compounds that modulate expression of tau protein or α-synuclein protein.

The present invention relates to new methods for the specific detection, quantification and / or differential diagnosis of neurodegeneration in an individual making use of a combination assay detecting at least three neurological markers in one or more body fluids of said individual, the type and degree of neurodegeneration being reflected in the quantitative changes in the level of all of said neurological markers compared to the control sample. The present invention also relates to methods for the detection of Rab3a, SNAP25 and alpha-synuclein in cerebrospinal fluid and to the use of these methods in a combination assay for specific detection, quantification and / or differential diagnosis of neurodegeneration.

Methods and diagnostic kits for determining whether a subject may develop a or for diagnosing a neurodegenerative disease. The method includes quantitating the amount of alpha-synuclein and total protein in a cerebrospinal fluid (CSF) sample obtained from the subject and calculating a ratio of alpha-synuclein to total protein content; comparing the ratio of alpha-synuclein to total protein content in the CSF sample with the alpha-synuclein to total protein content ratio in CSF samples obtained from healthy neurodegenerative disease-free subjects; and (c) determining from the comparison whether the subject has a likelihood to develop neurodegenerative disease or making a diagnosis of neurodegenerative disease in a subject. A difference in the ratio of alpha-synuclein to total protein content indicates that the subject has a likelihood to develop a neurodegenerative disease or has developed a neurodegenerative disease.

The invention describes antibodies having a high affinity for aggregated forms of α-synuclein and a low affinity for monomeric forms of α-synuclein. The antibodies are useful in the diagnosis of neurodegenerative diseases.

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Polyhydroxylated aromatic compounds, and compositions containing them, are useful for the treatment of amyloidosis, especially Alzheimer's disease, and for the treatment of diseases characterized by α-synuclein fibril formation, especially Lewy body disease and Parkinson's disease.

The application identifies fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

The present invention relates to combination therapies for treating Alzheimer's disease or an amyloidosis-associated pathological condition comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound. In certain embodiments, the first compound or the second compound inhibits AB peptide polymerization; is an anti-inflammatory; improves cognitive function, mood, or social behavior; is associated with Tau or alpha-synuclein; or regulates amyloid peptide washout.

Provided are human alpha-synuclein-specific autoantibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for α-synuclein are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for α-synuclein targeted immunotherapy and diagnosis, respectively.

Disclosed herein are antisense compounds and methods for decreasing alpha-synuclein mRNA and protein expression. Also disclosed herein are methods for treating, preventing, and ameliorating neurodegenerative diseases in an individual in need thereof.

The invention relates to novel monoclonal anti-alpha-synuclein antibodies. The antibodies can be used for treating a synucleinopathy such as Parkinson's disease (including idiopathic and inherited forms of Parkinson's disease), Diffuse Lewy Body Disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), Combined Alzheimer's and Parkinson disease, pure autonomic failure and multiple system atrophy.

Medical compositions and methods of treating or preventing neurodegeneration in a human suffering from or that is at risk of or susceptible to neurodegeneration or cellular dysfunction associated with expression or impaired cellular function of a neuronal protein encoded by one or more genes that code for alpha-synuclein (SNCA), Parkin RBR E3 ubiquitin protein ligase, (PARK2), Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase / (PINK1), Daisuke-Junko 1, (DJ-1) and ATPase type 13A2 (ATP13A2), are disclosed. Methods of treatment for these disorders is also provided, comprising administering a vector into a cell, wherein the vector facilitates expression of a molecular component that alters one of the aforementioned genes in the cell or expression of the gene in the cell, the gene being implicated in an etiology of the neurological deficit.

The invention relates to a method for external detection of polymerizing power of disease-related protein promoted by body fluids of subjects. More specifically, the invention concerns a method for detecting the oligomer formation power of disease-related protein such as alpha-synuclein promoted by body fluids of the subjects in vitro. The method comprises: incubating purified recombinant human disease-related protein and body fluids of the subjects by stirring at a certain temperature to make the two components be polymerized, and detecting the content of oligomers of disease-related protein such as alpha-synuclein in the incubated body fluids by utilizing a method that can detect protein oligomers. The method provided by the invention has advantages that: 1) the need for body fluid sample is less, so the subjects are easy to accept; 2) operations are simple; and 3) the result obtained from the detection method reflects the synthetic action of various factors of polymerization of disease-related protein to subjects, and the result is particularly more favorable for determining comprehensive pathophysiological situations of patients with Parkinson disease caused by complex factors.

Methods for identifying and characterizing inhibitors of protein filament formation are provided. These methods are particularly useful for identifying those agents which inhibit or prevent protein filament formation within neurons of mammalian subjects, particularly human subjects, such as the formation of tau filaments in Alzheimer's patients, and α-synuclein filaments in Parkinson's patients. According to the methods, protein monomers which are associated with formation of intra- or extra-cellular aggregates are combined under physiological conditions with a fibrillization inducer and the formation of protein aggregates is assessed in the absence and the presence of a test agent. The absence or a reduction in the size or stability of proteinaceous polymeric filaments as compared to a control indicates that the test agent is an inhibitor of proteinaceous polymeric filament formation.

Polynucleotide molecules and the proteins encoded by the molecules, diagnostic and treatment methods for neurological disorders characterized by protein aggregation are provided. Genes are described herein that affect the misfolding of, and subsequent aggregation of, aggregation-prone proteins such as alpha-synuclein and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation such as Parkinson's disease. Knockdown of expression of the genes described herein using RNAi results in alpha-synuclein protein aggregation in a C. elegans model of protein aggregation. Dopaminergic neuroprotection after exposure to the neurotoxin 6-OHDA or overexpression of alpha-synuclein may also be provided by overexpression of proteins. Knowledge of genes relating to protein misfolding and aggregation provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds to treat neurodegenerative diseases such as Parkinson's disease.

Biomarkers, methods, and systems for assessment of traumatic brain injury of different severities, as well as treatment efficacy and blood brain barrier or blood cerebrospinal fluid integrity and assessment of neurodegenerative conditions. The methods include detecting in a patient sample one or more of ubiquitin C-terminal hydrolase LI (UCH-L1), glial fibrillary acid protein (GFAP), aldehyde dehydrogenase 1 family member LI (ALDHILI), phosphorylated neurofilament heavy chain (pNFH), medium chain (NFM), or light chain (NFL), alpha-synuclein, visinin-like protein 1 (VILIP-1) and S100B.

Provided are human alpha-synuclein-specific autoantibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for α-synuclein are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for α-synuclein targeted immunotherapy and diagnosis, respectively.

The invention provides a peptoid as well as a preparation method and application thereof. The peptoid comprises the following subunits: ethylenediamine (I), piperonylamine (II), beta-alanine (III), 1-naphthylamine (IV) and cysteine (V). The peptoid is simple in synthesis, has strong combining capacity with alpha-synuclein, can effectively screen the serum of PD patients and able-bodied persons through alpha-synuclein in the serum, and provides a novel liquid biopsy method and concept for diagnosis and monitoring of the Parkinson's disease.

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.