51 results about "Fabry disease" patented technology

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

Provided are in vitro and in vivo methods for determining whether a patient with Fabry disease will respond to treatment with a specific pharmacological chaperone.

Methods of modulating uptake of extracellular lysosomal enzymes by administering a pharmaceutical agent and methods of treating a lysosomal storage disease (such as Gaucher disease, Pompe disease, Fabry disease or Niemann-Pick disease) or enhancing enzyme replacement therapy or gene therapy, comprising administering a pharmaceutical agent such as dexamethasone, glucose or insulin, are provided.

Provided are in vitro and in vivo methods for determining whether a patient with Fabry disease will respond to treatment with a specific pharmacological chaperone.

Methods of modulating uptake of extracellular lysosomal enzymes by administering a pharmaceutical agent and methods of treating a lysosomal storage disease (such as Gaucher disease, Pompe disease, Fabry disease or Niemann-Pick disease) or enhancing enzyme replacement therapy or gene therapy, comprising administering a pharmaceutical agent such as dexamethasone, glucose or insulin, are provided.

Compositions and methods for treating lysosomal storage diseases are disclosed. Lysosomal dysfunction is usually the result of deficiency of a single enzyme necessary for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides which are fated for breakdown or recycling. The compositions contain triplex-forming molecules which can be used to induce site-specific homologous recombination in mammalian cells when combined with donor DNA molecules, by stimulating cellular DNA synthesis, recombination, and repair mechanisms. The methods are particular useful for correcting point mutations in genes associated with lysosomal storage diseases such as Gaucher's disease, Fabry disease, and Hurler syndrome. Methods for determining the frequency of target gene repair and assessing the restoration of the enzymatic activity of corrected polypeptides are also disclosed. Ex vivo and in vivo methods of gene correction in patients are also provided.

Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and / or a longer lasting activity under both lysosomal conditions and in a serum environment.

The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.

The present invention is directed to the quantitation of GL3 in human urine which can be used for the diagnosis of Fabry disease as well as for the assessment of treatment efficacy thereof.

The present invention relates to a composition comprising a lysosomal enzyme conjugated to a negatively charged scavenger receptor ligand. In some embodiments, the lysosomal enzyme is conjugated to the scavenger receptor ligand by way of a linker. The present invention also relates to a composition comprising lysosomal enzyme encapsulated by a liposome, said liposome externally comprising a negatively charged scavenger receptor ligand. The invention further encompasses a method of treating a lysosomal storage disease with the compositions listed above. The invention further encompasses a method of treating a lysosomal storage disease with an acylated, acetylated, or aconitylated lysosomal enzyme.

Disclosed are methods for delivering an enzyme to a subject's brain or bone. The methods include administering a hyaluronidase to the subject and administering the enzyme to the subject. The hyaluronidase and the enzyme are administered to the subject under conditions effective to deliver the enzyme to the subject's brain or bone. Compositions and kits which include hyaluronidase and an enzyme are also disclosed, as are methods for increasing blood-brain barrier permeability in a subject. Also disclosed are methods, compositions, and kits for delivering genes or other nucleic acid molecules to a subject's brain or bone, as well as methods, compositions, and kits for delivering enzymes to a subject's tissues. The methods, compositions, and kits are disclosed as being useful in treating or preventing a variety of enzyme deficiency diseases, such as those affecting brain and / or bone, e.g., as Canavan's disease, Fabry disease, Gaucher's disease, various forms of mucopolysaccharidosis (e.g., Hurler's syndrome, Scheie syndrome, Hurler-Scheie syndrome, Sanfillippo A syndrome, Morquio A syndrome, Morquio B syndrome, etc.), Niemann-Pick disease, Schindler disease, and Pompe disease.

The invention provides methods, compositions and kits for enzyme replacement therapy as well as molecular constructs, cells, tissues and plants suitable for expressing recombinant enzymes. Similarly, the invention provides methods for recombinantly producing and orally administering certain metabolic or lysosomal enzymes such as acid alpha glucosidase (GAA) alone, in a pharmaceutical composition or with an activator protein (AGA). Also, the invention provides methods for treating a glycogen storage disease type II (GSDII) or acid maltase deficiency (AMD) or Pompe disease or Fabry disease.

The present invention provides a pharmaceutical composition comprising a protein having α-galactosidase activity for treating Fabry disease, which causes no allergic side effect, which is highly stable in blood (plasma) and which can readily be taken up by a cell of an affected organ. The pharmaceutical composition for treating Fabry disease of the invention comprises, for example, a protein which acquires an α-galactosidase activity through alteration of the structure of the active site of wild-type human α-N-acetylgalactosaminidase.

The present invention is in the field of Fabry disease and concerns a pathogenic factor allowing diagnosis of Fabry disease. In particular lyso-ceramide trihexosamide (lyso-CTH) has been found to function as a diagnostic marker for Fabry disease.

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and / or a longer lasting activity under both lysosomal conditions and in a serum environment.

The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.

The present invention relates to a pharmaceutical composition comprising glucosylceramide synthase inhibitor and a one or more pharmaceutically acceptable excipients. The present invention specifically relates to a sublingual pharmaceutical composition of eliglustat or a pharmaceutically acceptable salt thereof and a one or more pharmaceutically acceptable excipients. Moreover, the present invention further relates to a pharmaceutical composition of eliglustat or a pharmaceutically acceptable salt thereof which is used in the treatment of individual with lysozymal storage diseases selected from the group consisting of, Gaucher disease, Sphingolipidoses, Farber disease, Krabbe disease, Fabry disease, Schindler disease, Tay-Sachs disease and Niemann-Pick disease.

The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the α-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and / or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and / or restore deficient levels of GLA expression and / or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.

Deoxynojirimycin and deoxygalactonojirimycin derivatives according to the present invention are N-alkylated D-galacto, D-gluco- or L-ido-deoxynojirimycin with a linear methyloxypentyl group bearing various sidegroups and a non-fused bicyclic aromatic group (“X”) on the methyloxy-carbon. These compounds display an increased inhibitory potency towards GCS, and / or an increased inhibitory potency towards GBA2, and / or a decreased inhibitory potency towards GBA1, relative to known deoxynojirimycin derivatives of the same (D-gluco, L-ido or D-galacto) configuration. Therefore, compounds of the present invention are effective in the treatment of diseases which are associated with an irregular level of cytosolic or lysosomal glucosylceramide and / or higher glycosphingolipids, such as a lysosomal storage disorder, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis, Sialidosis, Niemann Pick disease type C and AMRF, or a symptom of one of the diseases collectively classed as metabolic syndrome, such as obesity, insulin resistance, hyperlipidemia, hypercholesterolemia, polycystic kidney disease, type II diabetes and chronic inflammation, or a neurodenegerative disorder, such as Parkinson disease or Lewy-body dementia.

A pathogenic factor in plasma as an improved therapy for Fabry disease.

The invention discloses a detection kit for alpha-galactosidase activity, and belongs to the field of biochemical detection. The detection kit comprises a reaction solution, a precipitant, a stop solution, a linear standard substance and a reference substance, wherein the linear standard substance is a 4-methylumbelliferone solution, and the reaction solution is a 4-methylumbelliferone acyl-alpha-D-galactoside solution. The kit can rapidly and accurately carry out in-vitro detection on the activity of alpha-galactosidase in a human blood sample, and can achieve the purpose of rapidly, conveniently and accurately assisting in diagnosing Fabry disease patients in batches by detecting a collected filter paper dry blood slice sample or a venous blood sample; and the kit is high in detection sensitivity, good in selectivity, strong in anti-interference capability, good in reproducibility, simple and convenient to operate, good in product stability and easy to use clinically.

The present invention relates to a novel method for preparing induced pluripotent stem cells (iPSCs) by introducing four genes, Oct-4, Sox2, Klf4, and Glial, into somatic cells. The present invention also relates to the iPSCs produced by the aforementioned method. Also provided is a process of drug selection for a heritable genetic disease by use of the iPSCs produced by the aforementioned method. In particular, wherein the inherited disease is Fabry disease. The present invention also relates to a method for treating Fabry-associated myocardiopathy in a subject in need thereof, and a method for determining prognosis in a subject with Fabry-associated myocardiopathy.

The present disclosure provides expression constructs comprising a GLA transgene encoding the at least one alpha-Gal A protein for use in expressing alpha-Gal A proteins and preventing, inhibiting or treating Fabry disease or one or more symptoms associated with Fabry disease.

The invention discloses a recombinant adeno-associated virus (AAV) vector, which comprises an AAVX capsid and a vector genome, and the vector genome comprises a nucleotide sequence for coding functional alpha-galactosidase A and a regulatory sequence for guiding the expression of the alpha-galactosidase A sequence in a host cell. The invention also discloses application of the recombinant adeno-associated virus vector to treatment of Fabry disease.

The present invention provides a pharmaceutical combination for treatment of Fabry disease and use thereof. The present invention relates to a pharmaceutical combination for treating Fabry disease, and the pharmaceutical combination includes (i) a protein which has mutations in an amino acid sequence of α-N-acetylgalactosaminidase and has α-galactosidase activity and (ii) an active site specific chaperone.

Disclosed herein are novel uses of a polyhydroxylated pyrrolidine for the manufacture of a medicament for treating Fabry disease (FD). Accordingly, the present disclosure provides a method of treating a subject having or suspected of having FD. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), a salt, an ester or a solvate thereof, wherein: R1 is H, or C1-3 amine optionally substituted with —COR2; R2 is alkyl or alkene optionally substituted with cycloalkyl or phenyl having at least one substituent selected from the group consisting of, halo, alkyl, haloalkyl, and alkoxyl; so as to ameliorate, alleviate mitigate and / or prevent symptoms associated with the FD. According to preferred embodiments of the present disclosure, the compound of formula (I) is a chaperon of a mutated human lysosomal α-galactosidase A (α-Gal A).