18 results about "Glucocerebrosidase" 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.

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.

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 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.

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.

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.

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.

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 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 application relates to the field of enzyme engineering, genetic engineering and biocatalysis, in particular to a glucoamylase mutant, a nucleic acid molecule encoding the mutant, a recombinant expression vector, a recombinant host cell and application. The glucoamylase mutant is obtained by mutating a wild-type glucoamylase with an amino acid sequence as shown in SEQ ID NO: 1, and the mutation sites include a mutation site related to heat resistance and / or a mutation site related to alkali resistance. The present application realizes the improvement of the enzyme activity of the glucoamylase mutant under high-temperature and alkaline conditions, and the preferred embodiments realize the synergistic improvement of heat resistance and alkali resistance, significantly reducing the cost and energy consumption of industrial production, and can be widely applied in the field of starch-based biomass catalytic conversion.

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.