43 results about "Trypsin deficiency" patented technology

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

The invention features compositions and methods comprising at least one compound selected from a proteasomal inhibitor, an autophagy inhibitor, a lysosomal inhibitor, an inhibitor of protein transport from the ER to the Golgi, an Hsp90 chaperone inhibitor, a heat shock response activator, a glycosidase inhibitor or histone deacetylase inhibitor that are useful for treating or preventing a protein conformation disease in a subject by correcting misfolded proteins in vivo. The compositions and methods can further comprise an 11-cis-retinal or 9-cis-retinal compound. Examples of protein conformation disorders and / or diseases may include retinitis pigmentosa, age-related macular degeneration, glaucoma, corneal dystrophies, retinoschises, Stargardt's disease, autosomal dominant druzen, Best's macular dystrophy, al -antitrypsin deficiency, cystic fibrosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, nephrogenic diabetes insipidus, cancer and / or Jacob-Creutzfeld disease.

Novel compounds, compositions, and methods of using and preparing the same, which may be useful for treating alpha-1 antitrypsin deficiency (AATD) are disclosed.

The methods and compositions of the invention find use in the clinical diagnosis of cholestasis related syndromes, particularly PFIC types 1, 2, and 3; BRIC types 1 and 2; Alagille syndrome, and alpha1-antitrypsin deficiency. The compositions of the invention include isolated nucleic acid molecules and oligonucleotide pairs suitable for use in amplifying regions of cholestasis related genes. Compositions of the invention include a cholestasis related gene resequencing microarray suitable for determining the nucleotide sequence of a region of a cholestasis related gene. Knowledge of the nucleotide sequence of one or more regions of a patient's cholestasis related gene allows diagnosis of the patient's syndrome.

The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.

A novel alpha-1 antitrypsin variant, a method of preparing the same, and use thereof are provided. The alpha-1 antitrypsin variant has excellent stability in the body and maintains an inhibitory effect on elastase activities because the blood half-life (t1 / 2) and the area under blood drug concentration vs. time curve (AUC) are remarkably increased by adding an N-glycosylation site in animal cells through amino acid mutation between 1st and 25th positions of the N-terminus of alpha-1 antitrypsin. Therefore, the alpha-1 antitrypsin variant can be useful in preventing or treating alpha-1 antitrypsin deficiency.

The present invention relates to methods and compositions for modulating the unfolded protein response. The method further relates to methods and compositions for the treatment and diagnosis of protein conformational diseases or disorders, including, but not limited to, α1-antitrypsin deficiency, cystic fibrosis, and autoimmune diseases and disorders. The invention further provides methods for modulating the unfolded protein response by modulating XBP1 mRNA splicing.

Disclosed herein are compounds of formula (I), and pharmaceutical compositions comprising the same. The compounds of formula (I) are neutrophilic inflammation inhibitors, thus, they are useful for treatment and / or prophylaxis of inflammatory diseases and / or disorders associated with abnormal activation of neutrophils, such as ARDS, ALI, COPD, lung fibrosis, chronic bronchitis, pulmonary emphysema, α-1 anti-trypsin deficiency, cystic fibrosis, idiopathic pulmonary fibrosis, liver injury, steatohepatitis, liver fibrosis, damages caused by ischemia and reperfusion, myocardial infarction, shock, stroke, and organ transplantation, ulcerative cholitis, vasculitis, SLE, sepsis, SIRS, arthritis, psoriasis, atopic dermatitis, and inflammatory skin diseases.

A composition for delivering a cargo to the cytoplasm of a cell, wherein the cargo treats Non-Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease, Diabetes Mellitus Type 1 and Type 2, Atherosclerotic Cardiovascular Disease, and Alpha 1 Antitrypsin Deficiency. In another embodiment, the composition comprises: an exosome; cargo located inside the exosome, wherein the cargo comprises short interference RNA (siRNA) that depletes sodium-glucose linked transporter active sites. In another embodiment, the composition comprises: an exosome; cargo location inside the exosome, wherein the cargo corrects the missense SERPINA1 mutation from ‘Z’ to ‘M’.

The present invention relates to a method for treating chronic lung disease, in particular alpha-1 antitrypsin deficiency or emphysema caused by alpha-1 antitrypsin deficiency, with a neutrophil elastase inhibitor. The invention also relates to a pharmaceutical composition comprising a neutrophil elastase inhibitor.

The present invention relates to pharmaceutical aerosols comprising a β-hairpin peptidomimetic of formula cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-), or a pharmaceutically acceptable salt thereof, having inhibitory activity against human neutrophil elastase. It further relates to solid or liquid pharmaceutical compositions and kits for preparing and administering such aerosols. The invention can be used for the prevention, management or treatment of pulmonary diseases, such as alpha-1 antitrypsin deficiency (AATD), cystic fibrosis (CF), non-cystic fibrosis bronchiactasis (NCFB), or chronic obstructive pulmonary disease (COPD), or infections, or diseases, or conditions of the lungs, being mediated by or resulting from human neutrophil elastase activity. Thus, the invention further relates to a pharmaceutical composition or a pharmaceutical aerosol comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neurophil elastase activity in a subject.

Methods of treating liver diseases are provided. Accordingly there is provided a method of treating a liver disease selected from the group consisting of fatty liver disease and chronic liver rejection in a subject in need thereof, wherein said liver disease is not associated with genetic alpha-1 anti-trypsin (AAT) deficiency, the method comprising administering to the subject a therapeutically effective amount of AAT.

A chimeric protein that is a fusion construct of a series of functional domains is used to deliver a therapeutic agent to a human subject suffering from disease. In some embodiments, the chimeric protein includes a therapeutic region, a transportation region, and a cleavage region disposed between the therapeutic region and the transportation region. The transportation region allows the chimeric protein to be moved across a cellular membrane of an affected cell within the subject. Cleavage of the chimeric protein at the cleavage region once within the cell separates the therapeutic region from the transportation region, enabling the therapeutic region to function normally within the cell. The therapeutic region can be effective in the treatment of, for example, muscular dystrophy, diastrophic dysplasia, malignant melanoma, porphyria, alpha-1 antitrypsin deficiency, Aicardi-Goutieres syndrome, cystic fibrosis, progeria, Marfan syndrome, tuberous sclerosis, adrenoleukodystrophy, and the like.

A kit for screening genetic liver diseases with high detection throughput, high sensitivity and strong specificity, the genetic liver diseases include progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, Congenital defects in bile acid synthesis, primary bile acid malabsorption, Dubin‑Johnson syndrome, hereditary hemochromatosis, alpha 1 antitrypsin deficiency, glycogen storage disease, autosomal recessive polycystic kidney disease, Budd Chiari syndrome , glycogen accumulation disease, etc. The genetic liver disease screening detects a total of 39 genes, namely ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, HSD3B7, AKR1D1, CYP7B1, AMACR, ABCD3, SLC10A2, ABCC2, HFE, TFR2, SERPINA1, G6PC, SLC37A4, AGL, PYGL, SLC40A1, PKHD1, F5, GYS2, VIPAS39, SLC25A13, JAG1, NOTCH2, PHKA2, PHKB, PHKG2, PHKA1, ALAD, HAMP, HFE2, SMPD1, ATP7B, ABCA1, NPC2, NPC1; the kit includes targeted capture probes SEQ NO: 1 to SEQ NO: 722 for all exons of 39 genes. The invention is used for gene detection.