31 results about "Cerebroside" patented technology

A genetically modified human beta-glucocerebrosidase (GCase) is disclosed. The genetically modified GCase comprises an amino acid sequence at least 85% identical to SEQ ID NO:2; contains mutations at positions L34P, K224N / G, T369E, and N370D corresponding to SEQ ID NO:2; and is capable of catalyzing the hydrolysis of the glycolipid glucosylceramide (GlcCer). Pharmaceutical compositions comprising the genetically modified GCase and therapeutic methods using the same are also disclosed.

Provided is a recombinant adeno-associated viral (rAAV) vector comprising one or two of (a) to (c): (a) a nucleotide sequence encoding aromatic L-amino acid decarboxylase (AADC), (b) a nucleotide sequence encoding glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF), such as cerebral dopamine neurotrophic factor (CDNF) or glial cell derived neurotrophic factor (GDNF), for treating neurodegenerative disorders, particularly Parkinson's disease (PD), Multiple system atrophy (MSA), Gaucher's disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vector, a pharmaceutical composition comprising the viral particles, and uses thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof, Lysosomal Membrane Protein 2 (LIMP2), Prosaposin, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Provided are compounds represented by formula (I) or stereoisomers or pharmaceutically acceptable salts thereof, a pharmaceutical composition containing same, and the use thereof as a β-glucocerebrosidase (GCase) allosteric modulator, preferably for treating neurodegenerative diseases.

Provided are recombinant adeno-associated virus (rAAV) vectors comprising one or two of (a) to (c): (a) a nucleotide sequence encoding an aromatic L-amino acid decarboxylase (AADC); (b) a nucleotide sequence encoding a glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF) such as a brain dopamine neurotrophic factor (CDNF) or a glial cell-derived neurotrophic factor (GDNF), for use in the treatment of neurodegenerative disorders, in particular Parkinson’s disease (PD), multiple system atrophy (MSA), Gaucher’s disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vectors, pharmaceutical compositions comprising the viral particles, and uses thereof.

A persistent encapsulation structure capable of preventing the degradation of bioactive substances, which encapsulation structure comprises a variety of encapsulation structure bodies (10), characterized by that the respective encapsulation structure body (10) has a polysaccharide structure (11) by which a plurality of bioactive substances (12) are encapsulated, wherein the bioactive substance (12) is selected from a group consisting of a bioactive fatty substance (121) and a bioactive non-fatty substance (122); that the polysaccharide structure (11) comprises at least one polysaccharide, wherein the at least one polysaccharide is first thoroughly mixed, then sheared at high pressure or homogenized at high speed and finally atomized dried, such that the polysaccharide structure (11) forms branched polysaccharides and linear polysaccharides which form a multitude of network structures; that the bioactive fatty substance (121) is selected from a group consisting of glycerophospholipids, sphingophospholipids, gangliosides, L-α- / glycerylphosphorylcholines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol, phosphatidylserines, phosphatidic acids, phosphatidylglycerol, ceramides, glucocerebrosides, glycolipids, cholesterols and fatty acid substances; and that the bioactive nonfatty substance (122) is selected from a group of coenzymes, vitamins, carotenes, carotenoids, curcuminoids, curcumin, curcumin extract, polyphenols, saponins, glycosides, terpenoids, ergothioneine, minerals, acid substances, functional polysaccharides, carbohydrates, functional proteins, peptides, amino acids and their derivatives.

The present application belongs to the field of medicine, and particularly relates to a class of cerebrosides and the use of the pharmaceutical composition thereof as an immunosuppressive agent in the preparation of a medicine for preventing or treating immune-related diseases.

This invention belongs to the field of exosome preservation technology and discloses a stabilizer composition for exosome cryopreservation and its application. The stabilizer composition for exosome cryopreservation provided by this invention consists of the following components and their amounts: phytosphingosine: 0.1%-0.2%; cerebroside sulfate: 0.05%-0.1%; trehalose: 2%-5%; lipid-soluble antioxidant: 0.01%-0.05%; HEPES buffer: 10-20 mM; metal ion chelating agent: 0.01%-0.05%. The composition of this invention forms a "gradient protection" through the membrane insertion of phytosphingosine and the shallow negative charge shielding of cerebroside sulfate, enabling stable cryopreservation of exosomes for more than one week with a bioactivity retention of >85%. This preservative is animal-free, easy to use, and effective, making it suitable for the clinical translation and practical application of exosomes.

Provided are recombinant adeno-associated virus (rAAV) vectors comprising one or two of (a) to (c): (a) a nucleotide sequence encoding an aromatic L-amino acid decarboxylase (AADC); (b) a nucleotide sequence encoding a glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF) such as a brain dopamine neurotrophic factor (CDNF) or a glial cell-derived neurotrophic factor (GDNF), for use in the treatment of neurodegenerative disorders, in particular Parkinson’s disease (PD), multiple system atrophy (MSA), Gaucher’s disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vectors, pharmaceutical compositions comprising the viral particles, and uses thereof.

The present disclosure is generally directed GCase polypeptides as well as fusion proteins and complexes comprising a GCase polypeptide and an antigen-binding domain that specifically binds to blood-brain barrier (BBB) target such as human transferrin receptor (TfR) or human CD98 heavy chain (CD98hc). Such fusion proteins and complexes can transport the GCase polypeptide across BBB, e.g. for treatment of GCase deficiencies in the central nervous system.

The present invention relates to modified β-glucocerebrosidase (GCase) polypeptides and polynucleotides comprising modified glucocerebrosidase (GBA) nucleotide sequences. The present invention further relates to viral particles comprising recombinant genomes comprising polynucleotides of the invention, and compositions comprising modified GCase polypeptides, polynucleotides, or viral particles of the invention. The present invention also relates to methods and uses of the modified GCase polypeptides, polynucleotides, viral particles, and / or compositions of the invention. The present invention further relates to modified GCase polypeptides, polynucleotides, viral particles, or compositions of the invention for use in a method of treatment or for use in the manufacture of a medicament for use in a method of treatment.

The present invention relates to the use of an active pharmaceutical ingredient N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-methylenimine acyl chloride and an acid addition salt thereof in the preparation of an oral medicament for the treatment of glucocerebrosidase (GBA)-related Parkinson's disease or GBA-related Parkinson's syndrome. The invention also relates to the use of the N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-methylenimine acyl chloride and the acid addition salt thereof.

The application is directed to compounds of formulae (IA) and (IB) and their salts and solvates, wherein R1a, R2a, R3a, A1, A2, A3, R1b, R2b, R3b, B1, and B2 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and / or prevention of, e.g., lysosomal storage diseases, such as Gaucher's disease, and α-synucleinopathies, such as Parkinson's disease.

A nucleic acid fragment comprising a nucleotide sequence encoding a human glucocerebrosidase (GCase) is provided. The invention also provides an expression vector containing the nucleic acid fragment, a recombinant adeno-associated virus (rAAV) containing the expression vector, a pharmaceutical composition containing the nucleic acid fragment, the expression vector or the rAAV, and application of the nucleic acid fragment, the expression vector or the rAAV in treatment of central nervous system diseases.

The present invention relates to recombinant DNA molecule encoding β-glucocerebrosidase (GCase) enzyme. The present invention also relates to recombinant DNA construct, recombinant vector, recombinant host cell, mRNA molecule, delivery system, pharmaceutical compositions and method of treating or managing symptoms of Gaucher disease in a subject.

A genetically modified human beta-glucocerebrosidase (GCase) is disclosed. The genetically modified GCase comprising an amino acid sequence at least 85 % identical to SEQ ID NO: 2; and comprising mutations at coordinates L34P, K224N / G, T369E and N370D, where the coordinates correspond to said SEQ ID NO: 2; and capable of catalyzing hydrolysis of a glycolipid glucosylceramide (GlcCer). Pharmaceutical compositions comprising the genetically modified GCase and therapeutic methods of using same are also disclosed.

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

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The application discloses a blood marker combination and kit for neurodegenerative diseases of lysosome function axis, and relates to the technical field of biomedical detection. The marker combination is composed of seven markers in three categories: glucocerebrosidase and cathepsin D; sphingolipids and gangliosides; and phosphorylated tau-217 protein, neurofilament light chain protein and glial fibrillary acidic protein. The application also provides an in-vitro diagnostic kit containing specific reagents for detecting the above markers, and constructs a risk assessment model based on a logistic regression or random forest algorithm. The marker combination and kit can be used for early screening, differential diagnosis, disease progression prediction and drug efficacy monitoring of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and neurogenic Gaucher disease, and have the advantages of high sensitivity, high specificity and minimally invasive detection.

Provided are a composition containing a lipid nanoparticle (LNP) and an mRNA, and use thereof in the treatment of Gaucher disease. The composition contains an LNP and an mRNA, and the mRNA is encapsulated in the LNP or associated with the LNP, wherein the mRNA contains a nucleotide sequence encoding GBA1. The composition can effectively increase the expression and activity of β-glucocerebrosidase (β-GCase) in the serum and multiple target organs of a subject, and reduce the level of glucosylsphingosine (Lyso-GL1) therein. In addition, the composition possesses a relatively long half-life and has application prospects in the treatment of Gaucher disease.

The present invention provides oligonucleotides that increase the expression of glucocerebrosidase (GBA) in a cell; conjugates, salts and pharmaceutical compositions thereof; and methods for treating diseases associated with reduced expression of GBA, including Gaucher's disease and / or Parkinson's disease. The oligonucleotide may comprise a contiguous sequence complementary to a contiguous base in the 3'untranslated region (UTR) of the GBA mRNA transcript.

This application provides methods of treating Krabbe disease, for example in an infant. Such methods can include immunosuppressing the patient, for example by administration of a myeloablative regimen, administering an umbilical cord blood transplant (UCBT) (such as an allogenic UCBT), and increasing expression of galactocerebrosidase (GALC) in the patient (e.g., by using gene editing).

Provided are recombinant adeno-associated virus (rAAV) vectors comprising one or two of (a) to (c): (a) a nucleotide sequence encoding an aromatic L-amino acid decarboxylase (AADC); (b) a nucleotide sequence encoding a glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF) such as a brain dopamine neurotrophic factor (CDNF) or a glial cell-derived neurotrophic factor (GDNF), for use in the treatment of neurodegenerative disorders, in particular Parkinson's disease (PD), multiple system atrophy (MSA), Gaucher's disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vectors, pharmaceutical compositions comprising the viral particles, and uses thereof.

The application relates to fluorescence-quenched substrates of Formula (I) for an acid β-glucosidase (GCase) and their use in a method for determining GCase activity in a cell or tissue, a method for localizing GCase activity within a cell, a method for determining the effect of a GCase modulator in a cell, a method for determining the efficacy if a GCase-directed therapy, and a method of screening for a GCase activity enhancer.

The present invention relates to an active pharmaceutical ingredient selected from N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride, its stereoisomers and the acid addition salts thereof (arimoclomol), for use in a method of treating glucocerebrosidase associated disorders.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof, Lysosomal Membrane Protein 2 (LIMP2), Prosaposin, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The present disclosure provides engineered glucocerebrosidases, polynucleotides encoding the engineered glucocerebrosidases, and methods of treating deficiencies in glucocerebroside activity using the engineered glucocerebrosidases or recombinant polynucleotides encoding the engineered glucocerebrosidases. The present disclosure further provides methods or uses of the engineered glucocerebrosidases or recombinant polynucleotides to treat conditions or diseases associated with deficiencies in glucocerebrosidase activity, such as Gaucher's disease.

A composition for preventing and / or improving brain dysfunction, especially Alzheimer's disease is provided. The composition includes dihydromyricetin or salts thereof, L-theanine, taurine, and cerebroside, which can enhance the intestinal stability and bioavailability of dihydromyricetin and prevent and improve brain dysfunction through multiple mechanisms such as anti-inflammation, inhibition of DNA methylation, elimination of hematoma, and removal of Aβ. In addition, the composition can be used in combination with monoclonal antibody drugs to reduce adverse reactions such as cerebral edema and cerebral hemorrhage that may occur during the treatment of Alzheimer's disease.

The present invention provides oligonucleotides, their conjugates, salts, and pharmaceutical compositions that increase the expression of glucocerebrosidase (GBA) in cells, as well as methods for treating diseases associated with reduced GBA expression, including Gaucher disease and / or Parkinson's disease. The oligonucleotides may contain a sequence of bases complementary to the sequence of bases in the 3' untranslated region (UTR) of the GBA mRNA transcript.