42 results about "Lysosomal storage disorders" patented technology

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 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.

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 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).

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 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.

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.

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

The present invention relates to pharmaceutical compositions and uses against lysosomal storage disorders. The present disclosure provides treatment for lysosomal storage disorders (LSDs) comprising administration of acetyl-leucine or a pharmaceutically acceptable salt thereof.

The present disclosure provides for treating neurodegenerative diseases and lysosomal storage disorders comprising administering leucine, or a pharmaceutically acceptable salt thereof for direct delivery in a subject in need thereof. The disclosure further provides for leucine, or a pharmaceutically acceptable salt thereof for direct delivery in a subject in need thereof, for example, in an elderly subject, to improve cognitive function, mobility, or cognitive function and mobility.

A number of medical disorders are caused by either an insufficiency of a gene product or a defective gene product. Gene therapy can be used to provide a sufficient amount of a gene product when a disorder is caused by an insufficiency and can also be used to inactivate genes that produce defective gene products. Examples of disorders that can be treated by providing a sufficient amount of a gene product include lysosomal storage diseases, clotting disorders, diabetes, and alpha-1 antitrypsin deficiency. Systems and methods to produce B cells that express selected antibodies and gene products are described. The systems and methods can be used to provide prolonged and tunable expression of the gene products for the treatment of diseases such as lysosomal storage diseases, clotting disorders, diabetes, or other protein deficiencies.

The present disclosure provides methods of treating lysosomal storage disorders such as Niemann-Pick Disease, Type-C, by administering a therapeutically effective amount of arimoclomol. The present disclosure further provides methods of removing lysosomal cholesterol by administering the same.

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 pharmaceutical compositions and uses against lysosomal storage disorders. The present disclosure provides treatment of lysosomal storage disease (LSD) comprising administering acetyl-leucine or a pharmaceutically acceptable salt thereof.

The present invention relates to lipid nanoparticles for the delivery of proteins and, specifically, to lipid nanoparticles for the intracellular or in vivo delivery of various medicinal proteins such as therapeutic proteins or enzymes for enzyme replacement therapy (ERT). The present invention can be advantageously used for the treatment and prevention of various diseases, including lysosomal storage disorders, by stably and effectively delivering various proteins such as therapeutic proteins or ERT enzymes into cells through lipid nanoparticles.

Provided are compositions comprising vectors for the co-expression of a modified GlcNAc-1- Phosphotransferase gene and a lysosomal enzyme. The gene encoding the lysosomal enzyme is operably linked to a first promoter and the gene encoding the GlcNAc-1 -Phosphotransferase is operably linked to a second promoter. Also provided herein are methods of treating a lysosomal storage disorder comprising administering to a subject the compositions of the disclosure.

The present disclosure provides compounds represented by Formula I:and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, and R3 are as defined as set forth in the specification. The present disclosure also provides compounds having Formula I for use to treat or prevent the progression of a lysosomal storage disorder or a neurodegenerative disease in a subject, provide neuroprotection in a subject having a lysosomal storage disorder, treat or prevent a migraine, and the symptoms associated therewith, in a subject, or improve mobility and / or cognitive function in a subject.

The present technology relates to methods of treating neurodegenerative diseases and disorder, such as lysosomal storage disorders, by administering a combination prodrugs of arimoclomol and prodrugs of miglustat. The present technology further provides methods of synthesizing said prodrugs and compositions comprising said prodrugs.

The invention discloses a gene interference vector as well as a construction method and application thereof in treating acute myelogenous leukemia. The pNM6-miGBA prepared by the invention can respond to the activity of NF-kappa B in acute myelogenous leukemia cells to the greatest extent, accurately and efficiently silence GBA, inhibit the enzymatic activity of GBA, accumulate GlcCer, induce lysosomal storage disorder and trigger multiform death, mainly ferroptosis, of the acute myelogenous leukemia cells, but has no significant toxicity to normal cells. The invention is expected to provide a new technology and a new reagent for the treatment of acute myelogenous leukemia.

The present invention provides methods for detecting multiple biomarkers indicative for lysosomal storage diseases from a dried blood spot. In particular, the present invention provides a method that is suited for detecting multiple biomarkers, each indicative for the presence of a distinct lysosomal storage disease in a subject, based on a single sample preparation procedure. In particular, the method allows simultaneous extraction of different biomarkers such as Lyso-Gb1 (GlcSph). Lyso-Gb3, and others from a dried blood spot sample. The invention further provides a kit of parts comprising means for conducting the methods subject of the invention. Finally, the invention provides a set of reference ranges for Lyso-Gb1 (GlcSph) and Lyso-Gb3 in healthy subjects starting from dried blot spot samples.

The present disclosure provides methods of treating lysosomal storage disorders such as Niemann-Pick Disease, Type-C, by administering a therapeutically effective amount of arimoclomol in combination with miglustat. The present disclosure further provides methods of removing lysosomal cholesterol by administering the same.

The invention relates to the use of nizubaglustat in treating a lysosomal storage disorder in a human subject. Specifically, the invention relates to the use of nizubaglustat at a dose of 3mg – 9mg total / day. The invention also relates to pharmaceutical compositions comprising nizubaglustat at a dose of 3mg – 9mg total / day.