51 results about "Fabry disease" patented technology

Provided are a compound having a 2,3-dihydro-1H-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same and a use thereof, where the compound having a 2,3-dihydro-1H-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.

Provided are a compound having a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof, of Formula 1a pharmaceutical composition comprising the same and a use thereof, where the compound having a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.

Described herein are novel engineered peptides, viral vectors, and pharmaceutical compositions thereof, and uses of the same for increasing α-GAL A expression and for the treatment of conditions associated with α-GAL A deficiency, such as Fabry disease.

A composition including a gene therapy delivery system and an alpha-galactosidase (GLA) polynucleotide encoding a GLA polypeptide, wherein the GLA polypeptide has at least 95% sequence identity to one of SEQ ID NOS. 1-40, 44-45, 51-52, 57, 61-173 or 212. Also provided are compositions, formulations, fusion proteins, and methods for the treatment of Fabry disease.

The present disclosure provides methods of treating lysosomal storage disorders, e.g., Fabry disease, Gaucher disease, Farber disease, and Pompe disease. The method comprises producing vector-transduced T-Rapa cells that express a transgene of interest and administering the cells to a patient in need thereof. The T-Rapa cells may be transduced with a dual promoter lentivirus vector.

A formulation for use in the treatment of Fabry disease, wherein the formulation comprises a carrier and 1-deoxygalactonojirimycin or a salt therof, characterized in that the 1-deoxygalactonojirimycin or a salt thereof is administered to a Fabry disease patient in an amount of 150 mg every other day.

The invention relates to the technical field of gene detection, in particular to a probe composition and a kit for screening various genetic disease related gene mutations and a preparation method of the probe composition and the kit. The hereditary diseases comprise 23 hereditary diseases such as citrullinemia type, hepatolenticular degeneration, 21-hydroxylase deficiency, progressive pseudohypertrophy muscular dystrophy, fragile X syndrome, Friedreich ataxia, glycogen accumulation disease type II, Gaucher disease, autosomal recessive deafness type 1A, Fabry disease, alpha-thalassemia, beta-thalassemia and the like. The probe composition disclosed by the invention can be used for simultaneously screening the specific mutation types of the various genetic disease related genes, and is more accurate, comprehensive, convenient, high in detection efficiency, simple and economical compared with the traditional screening.

To provide methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone.SOLUTION: The present invention exemplifies an in vitro method for determining α-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of α-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.SELECTED DRAWING: None

The present disclosure provides, among other things, gene therapy approaches of treating Fabry disease in a subject, particularly for alleviating periphery neuropathy associated with Fabry disease. The method comprises administering to a subject in need thereof a recombinant adeno-associated viral vector (rAAV) packaged in an AAV capsid having broad tissue tropism, and expressing a GLA transgene with improved stability and lowered immunogenicity.

The present invention relates to a lysosomal protein composition comprising a plurality of lysosomal proteins that are potentially diversely glycosylated according to a glycosylation pattern, wherein said glycosylation pattern has at least 45% paucimannosidic N-glycans; a method of manufacturing the lysosomal protein composition in a bryophyte plant or cell, and medical and non-medical uses of the lysosomal protein composition. E.g. the lysosomal protein can be α-Galactosidase for the treatment of Fabry Disease or β-Glucoceramidase for the treatment of Gaucher's Disease. The unique glycosylation results in improved therapeutic efficacy—surprisingly even without mannose-6-phosphate that is common for CHO cell produced lysosomal proteins.

Methods and materials for treating chronic cardiac disorders are provided herein. For example, methods and materials for using a dual guanylate cyclase A and B activator (e.g., a polypeptide having the sequence set forth in SEQ ID NO:1) to treat hypertrophic cardiomyopathy and other cardiac conditions, such as conditions associated with ventricular hypertrophy, atrial hypertrophy, ventricular remodeling, atrial remodeling, systolic and / or diastolic dysfunction, heart failure (e.g., heart failure with reduced ejection fraction, heart failure with mildly reduced ejection fraction, and heart failure with preserved ejection fraction), and other forms of chronic heart disease (e.g., Fabry disease, Noonan syndrome, Pompe disease, PRKAG2-related cardiomyopathy, Danon disease, Friedrich ataxia cardiomyopathy, amyloidosis, or desminopathy) are provided herein.

Provided are dosing regimens for the treatment of Fabry disease in a patient. Certain methods relate to the treatment of ERT-experienced or ERT-naïve Fabry patients. Certain methods comprise administering to the patient about 123 mg free base equivalent of migalastat for improving left ventricular mass and / or improving podocyte globotriaosylceramide.

The present disclosure provides compositions comprising isolated, e.g., recombinant, adeno-associated viruses (AAV) particles, comprising a liver tropic capsid protein, e.g., an sL65 capsid protein, for delivery of a GALprotein. The present disclosure also provides compositions comprising a first nucleic acid encoding a liver tropic capsid protein, e.g., an sL65 capsid protein, and a second nucleic acid comprising a transgene encoding a GAL protein. The present disclosure also provides methods for making an isolated, e.g., recombinant, AAV particles, and methods for delivering an exogenous GALprotein into a subject and / or methods for treating a subject having a GAL-associated disease or disorder, e.g., a lysosomal storage disorder, e.g., Fabry disease.

This disclosure to methods for treating or preventing particular symptoms and disorders which are associated with lysosomal storage diseases using quinuclidine compounds of formula (I), optionally in combination with enzyme replacement therapy. This includes pain, such as abdominal pain, and dermatological disorders, such as angiokeratoma, in a patient having a disease such as Fabry disease. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods.

The invention discloses a recombinant human alpha-GalA-mono Fc fusion protein as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention constructs the alpha-GalA-mono Fc fusion protein, the alpha-GalA-mono Fc fusion protein comprises human alpha-GalA and human IgG1mono Fc fragments, the expression level of the alpha-GalA-mono Fc fusion protein is higher than that of the alpha-GalA-Fc fusion protein, and the generation of aggregates is obviously reduced from 49% to 24%. In addition, the IgG1mono Fc part of the fusion protein disclosed by the invention can also play a role in prolonging the half-life period of the fusion protein and play a better therapeutic role. The alpha-GalA-mono Fc fusion protein disclosed by the invention provides a new scheme for clinical research and treatment of Fabry disease, and has a good application prospect.

Provided herein are polynucleotides comprising a nucleotide sequence encoding a biomolecule, such as human alpha-galactosidase A, a nucleotide sequence encoding a promoter, such as a hepatocyte-specific promoter or a hepatocyte-muscle cell bispecific promoter, or a nucleotide sequence encoding an expression cassette, such as a human alpha-galactosidase A expression cassette. Also provided herein are promoters, expression cassettes, vectors, host cells, gene delivery systems (e.g., recombinant viral particles, such as recombinant adeno-associated virus (AAV) particles and non-viral gene delivery systems), related pharmaceutical compositions, and methods of using the same. Such compositions and methods are particularly suitable for gene therapy, particularly for lysosomal storage disorders, including Fabry disease.

Provided are a compound having a 2,3-dihydro-1H-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof, where the. The compound having a 2,3-dihydro-1H-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.

Provided are methods of treating Fabry disease in a patient having severe renal impairment. A method for the treatment of Fabry disease in a patient having severe renal impairment, including administering to the patient about 50 mg to about 200 mg free base equivalent (FBE) of migalastat or salt thereof at a frequency of less than once every week. A method for the treatment of Fabry disease in a patient having severe renal impairment, including administering to the patient about 50 mg to about 100 mg free base equivalent of migalastat or salt thereof at a frequency of between about once every three days and about once every two weeks.

A polynucleotide is provided comprising a nucleotide sequence encoding a biomolecule (e.g., human α-galactosidase A), a nucleotide sequence encoding a promoter (e.g., a hepatocyte-specific promoter or a hepatocyte-myocyte dual-specific promoter), or a nucleotide sequence encoding an expression cassette (e.g., a human α-galactosidase A expression cassette). Furthermore, promoters, expression cassettes, vectors, host cells, gene delivery systems (e.g., recombinant adeno-associated virus (AAV) particles and recombinant viral particles such as nonviral gene delivery systems), related pharmaceutical compositions, and methods for using them are also provided. Such compositions and methods are particularly suitable for gene therapy, and especially for lysosomal storage disorders, including Fabry disease.

The present invention relates to a gradient microfluidic chip for drug screening, a drug screening method using same, and a drug screening method for preventing or treating Fabry disease by using same. More specifically, the present invention relates to a gradient microfluidic chip having a structure capable of culturing and differentiating organoids at four constant drug concentration gradients together with continuous medium flow. When the gradient microfluidic chip for drug screening according to the present invention is used, the physiological function of organoids is improved by inducing the vascularization and differentiation of the organoids, thereby enabling reproduction of an organ at a human body level better than existing organoids, nutrients and various concentrations of a drug are smoothly supplied, and drug permeability is increased. Thus, a concentration-dependent therapeutic effect of a drug can be confirmed with high drug sensitivity, and therefore the gradient microfluidic chip enables rapid and effective drug screening.

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.

One non-limiting and exemplary embodiment provides a system for supporting medical and pharmaceutical information personnel in charge (MR).SOLUTION: A) information of patients having a likelihood of suffering from Fabry's disease, and / or b) information of physicians having a likelihood of being able to diagnose and / or treat Fabry's disease to a medical and pharmaceutical information personnel in charge. Also provided are a method, apparatus, and program for predicting the likelihood that a patient is suffering from Fabry disease, and a method, apparatus, and program for predicting the likelihood that a doctor can diagnose and / or treat Fabry disease.SELECTED DRAWING: None

There is described a nucleic acid molecule comprising a nucleotide sequence encoding for a functional α-galactosidase A protein wherein the nucleotide sequence has at least 85% identity to the sequence of SEQ ID NO. 1. Also described is a vector, host cell or transgenic animal comprising the nucleic acid molecule; and a pharmaceutical composition comprising the nucleic acid molecule or the vector. Further, the use of the nucleic acid molecule in a method of treating Fabry disease is described.

The invention relates to a composition comprising a synergistic combination of fluoroethylnormemantine (FENM) and at least one agonist or positive modulator of the sigma-1 receptor.More particularly, the invention relates to said composition for its use as a medicinal product, even more particularly for its use in the treatment of a selected pathology from among neurogenetic diseases of metabolic origin such as GM2 ganliosidosis, Krabbe disease, Fabry disease, sialidosis type I, Gaucher disease, Niemann-Pick disease type C, Refsum disease, cerebrotendinous xanthomatosis, adrenoleukodystrophy, or tauopathies, synucleinopathies, amyloidopathies, Alzheimer's disease, Parkinson's disease, multiple system atrophy, Huntington's disease, posterior cortical atrophy, Pick's disease, epilepsy, vascular dementia, frontotemporal dementia, Lewy body dementia, amyotrophic lateral sclerosis. Figure to be published with the abbreviation: FIGURE 5.

Polypeptide variants of human alpha-Gal A, codon-optimized coding sequences for the polypeptide variants and wild-type protein, and recombinant adeno-associated viral (rAAV) vectors comprising the coding sequences are provided. Also provided are chimeric promoters that can drive high expression in the liver and heart, which are suitable for use in the rAAVs of the present application.

The present disclosure relates to the methods for treating or ameliorating one or more symptoms of Fabry disease, reducing the amount of glycosphingolipids, and / or increasing an α galactosidase A (α-Gal A) protein activity in a subject in need thereof by administering the expression vectors (e.g., an AAV expression vector) comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an α galactosidase A (α-Gal A) transgene encoding the at least one α-Gal A protein at a dose of about 5×1012 vector genomes per kilogram of body weight (vg / kg) to about 5×1013 vg / kg.

To provide means to treat a patient with Fabry disease.SOLUTION: The present invention provides a pharmaceutical composition for treating a patient with Fabry disease, containing 1-deoxygalactonojirimycin or a salt thereof in a therapeutically effective dose of 150 mg, where the pharmaceutical composition is administered to the patient every other day.SELECTED DRAWING: None

Described herein are novel engineered peptides, viral vectors and pharmaceutical compositions thereof, and their use in increasing alpha-GAL A expression and treating diseases associated with alpha-GAL A deficiency, such as Fabry disease.

To provide methods and compositions for treatment of Fabry disease.SOLUTION: The present disclosure provides expression constructs comprising a GLA transgene encoding the at least one α-Gal A protein for use in expressing α-Gal A proteins and preventing, inhibiting or treating Fabry disease or one or more symptoms associated with Fabry disease. Disclosed herein is a method of expressing at least one α galactosidase A (α-Gal A) protein in a cell. In some embodiments, the method comprises administering an expression construct comprising a mutated WPRE sequence, optionally a mut6 mutated WPRE sequence, and a GLA transgene encoding at least one α-Gal A protein to the cell such that the α-Gal A protein is expressed in the cell.SELECTED DRAWING: None

Provided are a compound of Formula 1 having a chromane, isochromane, thiochromane, or tetrahydroquinoline moiety or pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof, wherein the compound having a chromane, isochromane, thiochromane, or tetrahydroquinoline moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.: