19 results about "Multisystem atrophy" patented technology

Disclosed is a method of treating a neurodegenerative disease such as Parkinson's disease, diffuse Lewy body disease, transitional Lewy body dementia, and multiple system atrophy in a subject. The method comprises administering to the subject a therapeutically effective amount of a peptide comprising an α-synuclein binding domain operably linked to a protein transduction domain and a proteasomal targeting domain, wherein the α-synuclein binding domain is derived from a reversed sequence of β-synuclein. Other methods, as well as uses and compositions, are disclosed.

The present disclosure relates to a method for diagnosing and treating multiple-system atrophy (MSA) in a subject, the method comprising: determining in a subject-derived biological sample an expression level of a gene from the group consisting of: QKI, GGCX, MOCS1, NF1, LINC01572, PRRG3, HMBOX1, PLP1, PPP1CA, C8orf88, TGFB2, MASP1, TIAM1, SYNGAP1, ACTN1, EMP1, NFIL3, GPNMB, PGAM2, ST5, STON1, RFTN1, and MMP14; comparing the subject-derived expression level of the gene with a normal control expression level of the gene obtained from a non-neurodegenerative biological sample; diagnosing the subject as a having MSA by detecting a differential expression of the gene in the subject-derived biological sample as compared to the normal control expression level; and administering a peroxisome proliferator-activated receptor β (PPARβ) agonist or a retinoid X receptor (RXR) agonist to the subject diagnosed as having MSA.

The invention relates to a multi-system atrophic animal model with abnormal blood pressure regulation and a construction method of the multi-system atrophic animal model, and belongs to the technical field of biology. The invention provides a construction method of a multi-system atrophy animal model with abnormal blood pressure regulation, and the construction method comprises the following steps: injecting recombinant adeno-associated virus of alpha-synuclein specifically expressed by oligodendroglia cells into a target brain region of an experimental animal to obtain the multi-system atrophy animal model, the multi-system atrophy modeling target brain region is a medulla oblongata head end abdominal lateral region. Researches prove that the animal model constructed by using the construction method can replicate the performance of upright hypotension in multi-system atrophy, and has typical pathological characteristics and behavior characteristics of multi-system atrophy. Therefore, the construction method and the constructed animal model have wide application prospects in research of multi-system atrophy and screening of related therapeutic drugs.

This application relates to a blood biomarker for the differential diagnosis of patients with Parkinson's disease and multiple system atrophy, and its uses. The blood biomarker contains at least SERPINA3. This blood biomarker can assist in the early diagnosis and continuous monitoring of patients with Parkinson's disease and multiple system atrophy. It is low-cost, simple to operate, fast to detect, minimally invasive, and readily accessible, making it suitable for most patients and possessing high clinical application value.

The present application relates to novel compounds of formula (I) or detectably labeled compounds thereof, stereoisomers, racemic mixtures, pharmaceutically acceptable salts, hydrates or solvates, which are useful for imaging and determining the amount of alpha-synuclein aggregates. Furthermore, the compounds may be used to diagnose a disease, disorder, or disorder associated with alpha-synuclein aggregates (e.g., Parkinson's disease or e.g., multi-system atrophy (MSA)), to determine susceptibility to the disease, disorder, or disorder, to predict prognosis of the disease, disorder, or disorder, to monitor disease progression in a patient suffering from the disease, disorder, or disorder, and to diagnose a disease, disorder, or disorder associated with alpha-synuclein aggregates. The progression of such diseases, disorders or abnormalities is monitored and the responsiveness of patients suffering from such diseases, disorders or abnormalities to their treatment is predicted.

A composition for preventing or treating synucleinopathies, which includes efavirenz or a salt or solvate thereof and a pharmaceutically acceptable carrier, is provided. The composition is useful in preventing or treating synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, because the composition serves to hinder cell-to-cell transmission of alpha-synuclein, prevent intracellular aggregation of α-synuclein, and inhibit transmission of aggregated α-synuclein.

FIELD: neurology; laboratory diagnostics.SUBSTANCE: used for the differential diagnosis of Parkinson's disease not associated with mutations in the GBA1 gene, and multiple system atrophy. The patient's peripheral venous blood is collected, from which mononuclear cells are isolated by gradient centrifugation, followed by their differentiation into a primary culture of macrophages in the presence of the macrophage colony-stimulating growth factor M-CSF to ensure proliferation and differentiation of monocytes into mature macrophages. The obtained blood macrophage cells are applied to 903 filter cards at a concentration of 2×106 cells / ml. Whatman 903 Sample Collection Cards can be used as 903 filter cards. The activity of lysosomal enzymes is determined: glucocerebrosidase GCase, alpha-galactosidase GLA, acid sphingomyelinase ASMase, galactosylceramidase GALC by high-performance liquid chromatography in combination with tandem mass spectrometry. The value of the canonical linear discriminant function CLDF is calculated using the stated formula. If the value of CLDF is ≥ 43.44, the patient is diagnosed with multiple system atrophy. If the value of CLDF is < 43.44, Parkinson's disease is diagnosed in patients who do not have a mutation in the GBA1 gene.EFFECT: method enables reliable and accurate differential diagnosis of Parkinson's disease and multiple system atrophy by assessing the activity of lysosomal enzymes.2 cl, 2 dwg, 2 ex

A method is provided for distinguishing between and / or diagnosing Parkinson's disease (PD) or multiple system atrophy (MSA) in a subject who is exhibiting symptoms associated with both PD and MSA. The method comprises: (A) contacting a biological sample obtained from the subject and comprising soluble, misfolded alpha-synuclein (αS) protein with a pre-incubation mixture comprising a monomeric αS substrate and an indicator to form an incubation mixture; (B) conducting an incubation cycle two or more times on the incubation mixture to form misfolded αS aggregates; (C) subjecting the incubation mixture to excitation and detecting via indicator fluorescence emission the misfolded αS aggregates; and (D) diagnosing the subject has having PD or MSA depending on the fluorescence emission intensity. In some aspects, the incubation cycles are conducted in the presence of a bead.

The present invention relates to agents, uses and methods for the treatment of synucleinopathies, in particular to novel monoclonal anti-alpha-synuclein antibodies. These antibodies can be used to treat synucleinopathies, such as Parkinson's disease, including idiopathic and genetic forms of Parkinson's disease, diffuse Lewy body disease (DLBD), Lewy body variants of Alzheimer's disease (LBV), combinatorial Alzheimer's and Parkinson's disease, pure autonomic failure, and multi-system atrophy.

The invention relates to the field of animal models, in particular to a preparation method of a fast eye movement sleep behavior disorder animal model with cytopathology specificity, which comprises the following steps: injecting adeno-associated virus for inducing neuronal overexpression alpha-synuclein into a capped karyobrain area on the back and the outer side of a non-human tested animal, and injecting the neuron-derived extracellular vesicles or the oligodendroglia-derived extracellular vesicles into the capped karyocerebral region on the back outer side of the non-human tested animal again. The model prepared by the method disclosed by the invention has the disease characteristics of fast eye movement sleep and has the characteristic that Parkinson-like phenotype is transformed. The model disclosed by the invention can be used for researching the etiology and pathological mechanism of transformation of rapid eye movement sleep behavior disorder to Parkinson's disease or multi-system atrophy and screening prevention and treatment drugs, and has remarkable significance for clinically providing effective drug treatment targets and prevention and treatment means.

The present invention relates to novel monoclonal anti-alpha-synuclein antibodies. These antibodies can be used to treat synucleinopathies, such as Parkinson's disease (including idiopathic and genetic forms of Parkinson's disease), diffuse Lewy body disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), combined Alzheimer's and Parkinson's disease, pure autonomic failure, and multiple system atrophy.

A method is provided for distinguishing between and / or diagnosing Parkinson's disease (PD) or multiple system atrophy (MSA) in a subject who is exhibiting symptoms associated with both PD and MSA. The method comprises: (A) contacting a biological sample obtained from the subject and comprising soluble, misfolded alpha-synuclein (αS) protein with a pre-incubation mixture comprising a monomeric αS substrate and an indicator to form an incubation mixture; (B) conducting an incubation cycle two or more times on the incubation mixture to form misfolded αS aggregates; (C) subjecting the incubation mixture to excitation and detecting via indicator fluorescence emission the misfolded αS aggregates; and (D) diagnosing the subject has having PD or MSA depending on the fluorescence emission intensity. In some aspects, the incubation cycles are conducted in the presence of a bead.

The present disclosure provides methods, compounds, compositions, formulations, or medicaments for treating, preventing, inhibiting, ameliorating, or delaying the onset of a- synucleinopathies (e.g., Parkinson's disease (PD), PD with dementia (PDD), dementia with Lewy bodies (LBD), or Multiple System Atrophy (MSA)) as well as methods for ameliorating, inhibiting, or delaying the onset of signs or symptoms of an a-synucleinopathy in a subject. The disclosed methods, compounds, compositions, formulations, or medicaments are also useful for addressing the related signs and symptoms of a- synucleinopathies. The methods comprise administering to the subject the compounds, mixtures of compounds, or compositions, formulations, or medicaments derived from said compounds or mixtures thereof to thereby produce the aforementioned therapeutically beneficial effect(s).

The present application relates to a kind of animal model of dysregulation of blood pressure multiple system atrophy and its construction method, belong to biotechnology field.The present application provides a kind of construction method of dysregulation of blood pressure multiple system atrophy animal model, the construction method includes: experimental animal target brain area is injected with the recombinant adeno-associated virus of oligodendrocyte specific expression alpha-synuclein, obtains multiple system atrophy animal model;The multiple system atrophy modeling target brain area is the ventral area of medulla oblongata head end.The research confirms, the animal model obtained using the construction method can be copied the performance of orthostatic hypotension in multiple system atrophy, and has the typical pathological characteristics and behavior characteristics of multiple system atrophy.Therefore, the construction method and the animal model obtained using the construction method have wide application prospect in the research of multiple system atrophy and the screening of related therapeutic drugs.

The invention particularly discloses a differential diagnosis marker for multi-system atrophy and Parkinson's disease and application of the differential diagnosis marker, and relates to the technical field of biomedicine. The invention provides a differential diagnosis marker for multi-system atrophy and Parkinson's disease, the differential diagnosis marker comprises APOE, APOD, HBA1 / HBA2, KLKB1, HBB and GC, when the differential diagnosis marker provided by the invention is used for diagnosis, AUC is obtained to be 0.719.

The present invention relates to methods of identifying subjects suffering from Multiple System Atrophy (MSA) or Parkinson's Disease (PD). The method comprises subjecting a biological sample obtained from a subject to a seeded aggregation assay or a sequence of seeded aggregation assays. The invention also further provides methods of treating the identified MSA patient or the PD patient with compounds capable of inhibiting alpha synuclein aggregation.

The invention provides crystalline 5,7-dimethyl-N-((1S*,4S)-4-(pentyloxy)cyclohexyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, compositions containing the crystalline compound, methods for making the crystalline compound, medical kits, and methods for using the crystalline compound and compositions to treat a medical disorder, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient.

Disclosed are a small molecule binding ligand of a α-synuclein aggregate, and a preparation method therefor and a use thereof. The small molecule binding ligand of a α-synuclein aggregate is a compound shown in the following general formula (I). The compound can specifically and strongly bind to a α-synuclein aggregate and can be used for detecting / dyeing the α-synuclein aggregate and Lewy body in the brain of a patient, and a radioactive marker of the compound can be used as an imaging tracer probe required in image examination technologies such as PET and SPECT for clinical disease diagnosis. The compound is further used for preparing the radioactively marked imaging tracer probe or a composition thereof. Diseases associated with α-synuclein misfolding and abnormal aggregation comprise Parkinson's disease, Parkinson's disease dementia, Alzheimer's disease, multiple system atrophy, Lewy body dementia, etc.

The present invention is directed to activators of TMEM175 Ion Channel, which are compounds of Formulae: (AAA), (AA), (A), (I), (II), (III), (IV), (V), (VI), (B), (B-I), and (B-II). The activators described herein can be useful in the treatment of diseases or disorders associated with disfunction of TMEM175 Ion Channel, such as Neurological Disorders, Parkinson's Disease, Alzheimer's disease, dementia with Lewy bodies (DEB), multisystem atrophy (MSA), progressive supranuclear palsy (PSP). In particular, the invention is concerned with compounds and pharmaceutical compositions activating TMEM175 Ion Channel in a cell, methods of treating diseases or disorders associated with disfunction of TMEM175 Ion Channel, and methods of synthesizing these compounds.