76 results about "Lysosomal storage disorders" patented technology

Aspects of the disclosure relate to bicistronic AAV nucleic acid constructs comprising a transgene encoding hexosaminidase A (HEXA) and hexosaminidase (HEXB) proteins. In some embodiments, the disclosure provides methods for treating or preventing lysosomal storage disorders, such as Tay-Sachs disease and Sandhoff disease, using bicistronic nucleic acid constructs described by the disclosure.

Provided herein are compositions and methods of using a bicistronic vector for treating or preventing a lysosomal storage disorder (LSD) in a subject. The disclosed compositions comprise a bicistronic vector comprising a promoter, an Internal Ribosome Entry Site (IRES), a polynucleotide encoding a lysosomal enzyme and a polynucleotide encoding a modified GlcNAc-1 phosphotransferase (GlcNAc-1 PTase). The present methods comprise administering to the subject a pharmaceutical composition comprising the bicistronic vector as disclosed herein.

The present disclosure provides methods of increasing cellular production of Niemann-Pick Disease, Type-C, Protein 1 (NPC1) in a patient in need thereof by administering a therapeutically effective amount of arimoclomol in combination with miglustat. The present disclosure further provides methods of reducing and / or delaying progression of Niemann-Pick Disease, Type-C in said patients.

The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment or prophylaxis of lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and / or other glucosylceramide-based glycosphingolipids (GSLs).

Aspects of the disclosure relate to compositions and methods for the treatment of lysosomal storage disorders, such as GM1 gangliosidosis, Tay Sachs disease, and Sandhoff disease. In some embodiments, the compositions comprise viral vectors encoding beta-galactosidase. In some embodiments, the compositions comprise viral vectors encoding beta-hexosaminidase subunits (e.g. HEXA, HEXB, or combinations thereof).

The invention relates to means and methods for gene therapy of lysosomal storage disorders (LSDs), preferably a LSD with skeletal involvement, based on an ex vivo gene therapy approach comprising transduction of autologous hematopoietic stem and progenitor cells (HSPCs) with viral vectors for expressing enzymes that are deficient in the disorders. The final formulation is a suspension of transduced cells in culture medium for the administration to patients affected by the LSDs, preferably preceded by a conditioning regimen.

Provided are substrates and methods for detecting enzymatic activity of various lysosomal storage enzymes. The molecules may be used as substrates with improved solubility.

Provided herein are compounds that inhibit glucosylceramide synthase (GCS). Also provided are pharmaceutical compositions comprising the compounds, and methods of treating diseases and disorders associated with GCS activity, such as lysosomal storage disorders.

The invention relates to constitutively active mutants of the transcription factor TFEB, which can mutate the lysine of one or both sites of positions 219 and 347; and / or also mutate the glutamic acid of one or both sites of positions 221 and 349, in order to eliminate the SUMOylation of the protein. By replacing these residues either from positions 219 and / or 221 and / or 347 and / or 349 by any other amino acid (such as arginine or alanine), it gives rise to a mutated TFEB, which more actively induces the expression of genes and protein synthesis of the lysosomal and autophagic pathway. Such as lysosomal storage disorders, neurodegenerative diseases, liver diseases, muscle diseases and metabolic diseases, and / or disorders or processes in the aging of the skin.

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

To provide improved methods for treating lysosomal storage disorders (LSDs).SOLUTION: The present invention provides acetyl-leucine, or a pharmaceutically acceptable salt thereof, for use in a method of treating a lysosomal storage disorder (LSD) or one or more symptoms associated with a LSD in a subject in need thereof, wherein the LSD is not Niemann-Pick Type C.SELECTED DRAWING: Figure 9A

Provided are molecules and methods for detecting enzymatic activity of various lysosomal storage enzymes. The molecules may be used as internal standards that may be combined with substrates that have improved solubility.

Disclosed herein are compounds that stabilize recombinant human α-iduronidase (rh-α-IDUA) activity, and their uses in the treatment and / or prophylaxis of lysosomal storage diseases (LSDs), such as mucopolysaccharidosis type I (MPS1). The compound disclosed herein has the structure of formula (I),wherein, n is an integral between 0 and 2; X1 is O or —NH; X2 is O, —NH or —NRa, inwhich Ra is C1-10alkyl; Y is H orwherein m and p are independently 0 or 1; X3 is S, O, or —NH; X4 is O, —NH, methylene, or —CH2(C1-10)alkyl; and A is aryl, heteroaryl, or heterocyclyl optionally substituted with one or more substituent selected from the group consisting of halo, hydroxyl, amino and phosphate.

Provided herein are compositions and methods using a bicistronic vector for treating or preventing a lysosomal storage disease (LSD) in a subject. The disclosed compositions include a bicistronic vector comprising a promoter, an internal ribosome entry site (IRES), a polynucleotide encoding a lysosomal enzyme, and a polynucleotide encoding a modified GlcNAc-1 phosphotransferase (GlcNAc-1 PTase). The method includes administering to a subject a pharmaceutical composition comprising the bicistronic vector disclosed herein.

The present invention provides novel fluorinated cyclic derivatives of sulfonamides and sulfones, compositions thereof, and methods for preparing and using them, which are useful for treating various diseases and disorders related to TRPML activity, such as neurodegenerative diseases, lysosomal storage disorders, muscular dystrophy, common neurodegenerative diseases associated with aging, diseases associated with oxidative stress or reactive oxygen species (ROS), and aging.

Aspects of the disclosure relate to compositions and methods for the treatment of lysosomal storage disorders, such as GM1 gangliosidosis, Tay Sachs disease, and Sandhoff disease. In some embodiments, the compositions comprise viral vectors encoding beta-galactosidase. In some embodiments, the compositions comprise viral vectors encoding beta-hexosaminidase subunits (e.g. HEXA, HEXB, or combinations thereof).

Compositions which treat lysosomal deficits in lysosomal storage disorders, neuronal ceroid lipofuscinosis, idiopathic / sporadic brain disorders that include neurological and psychiatric disorders, include agents such as troglitazone, rosuvastatin, Compound A or the combination thereof.

The present disclosure provides methods of increasing removal of lysosomal cholesterol in a patient in need thereof by administering a therapeutically effective amount of arimoclomol. The present disclosure further provides methods of reducing and / or delaying the progression of Niemann-Pick Disease, Type C, in said patients.

The present disclosure provides methods of increasing removal of endosomal cholesterol in a patient in need thereof by administering a therapeutically effective amount of arimocloml in combination with miglustat. The present disclosure further provides methods of reducing and / or delaying progression of Niemann-Pick Disease, Type-C, in said patients.

The present invention provides methods for treating lysosomal storage disorders such as Gaucher's disease, by using compounds of Formula III as described herein.

The present invention pertains to a novel treatment of pathologies caused by an increased synthesis or accumulation of sulfolipids such as sulfatide. The invention provides mutated arylsulfatase A (ARSA or ASA, EC 3.1.6.8) enzymes with increased activity towards sulfatide metabolization. The invention provides nucleic acids encoding the mutant ARSA, the use of the proteins and nucleic acids, as well as pharmaceutical compositions comprising them, in the treatment of lysosomal storage disorders (LSDs) such as metachromatic leukodystrophy (MLD).

The present invention relates to methods and materials useful for systemically delivering polynucleotides across the blood brain barrier using adeno-associated virus as a vector. For example, the present invention relates to methods and materials useful for systemically delivering α-N-acetylglucosamidinase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of these methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIB. As another example, the present invention relates to methods and materials useful for systemically delivering N-sulphoglucosamine sulfphohydrolase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of this second type of methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIA.

The present disclosure provides methods of increasing cellular production of Niemann-Pick, Type-C, Protein 1 (NPC1) in a patient in need thereof by administering a therapeutically effective amount of arimoclomol. The present disclosure further provides methods of reducing and / or delaying Niemann-Pick Disease, Type-C, progression in said patient.

Aspects of the invention relate to recombinant adeno-associated viruses (rAAVs). In some aspects, the rAAVs comprise artificial genetic regulatory elements that modulate transgene expression. In some aspects, the disclosure relates to the treatment of lysosomal storage disorders.

Provided herein are compositions and methods for treating or preventing a neurodegenerative disease, a myodegenerative disease, a prion disease, or a lysosomal storage disease in a subject.

The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment or prophylaxis of lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and / or other glucosylceramide-based glycosphingolipids (GSLs).

Provided herein are compositions and methods for treating or preventing a neurodegenerative disease, a myodegenerative disease, a prion disease or a lysosomal storage disease in a subject.

The present disclosure provides for treating lysosomal storage disorders (LSDs) comprising administering acetyl-leucine or a pharmaceutically acceptable salt thereof.

The present disclosure provides a treatment for lysosomal storage disorders (LSDs) comprising administration of acetyl-leucine or a pharmaceutically acceptable salt thereof.

Pompe disease is an autosomal recessive lysosomal storage disorder caused by mutations in the gene encoding acid alpha-glucosidase (GAA). This disclosure provides engineered acid alpha-glucosidase polypeptides, recombinant polynucleotides encoding engineered acid alpha-glucosidase polypeptides, and methods for using engineered acid alpha-glucosidase polypeptides and recombinant polynucleotides for therapeutic purposes. This disclosure provides acid alpha-glucosidase polypeptides engineered to have improved properties, in particular, compared to naturally occurring human acid alpha-glucosidase.