This disclosure describes methods and compositions for detecting the presence of autoantibodies associated with autoimmune polyglandualar syndrome 1 (APS1) in a biological sample. In particular, detection of APS1-specific autoantibodies that specifically bind to certain APS1 associated autoantigens in such methods is described. Also provided are methods of treating subjects with APS1 or at risk of developing APS1 associated conditions. Also provided are devices and kits useful for the diagnosis and prognostic assessment of subjects having APS1 and for assessing subject risk at developing particular APS1-associated conditions.

The present invention provides for compounds and methods for the detection and follow-up of Fabry disease (FD). In particular, the present invention relates to a method for detecting or diagnosing FD in a subject, comprising detecting globotriaosylceramide (Gb3) deposits in biomaterial obtained from said subject. The present invention also provides for a method for treatment monitoring of FD in a subject. Further, the present invention relates to the use of a Gb3-specific natural ligand for the detection of Gb3 deposits in biomaterial. Also provided is a kit for detecting Gb3 deposits in biomaterial obtained from a subject.

Improved methods and systems for diagnosing and for treating Cushing's syndrome and Cushing's Disease are provided herein, including methods and systems for concurrently treating Cushing's syndrome and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome in a patient with an established diagnosis of ACTH-dependent Cushing's syndrome. Treatment methods can use glucocorticoid receptor antagonists (GRAs), which differentially affect the ratio of cortisol to ACTH levels in patients having Cushing's Disease versus patients having Ectopic Cushing's Syndrome. Methods for concurrently treating and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome include obtaining baseline cortisol and ACTH levels of a patient, treating the patient with a GRA according to a protocol that would typically substantially elevate cortisol levels, obtaining post-treatment cortisol and ACTH levels of the patient, determining a differential relationship between baseline cortisol and ACTH levels and post-treatment cortisol and ACTH levels and providing a positive diagnosis based on the differential relationship.

The present invention relates to a method of providing a FAS finding (30) for the functionality of an anorexigenic signal path for a patient, comprising the steps: providing a sample matrix (10) of a body substance of the patient, determining at least one first FAS indicator (11) from the sample matrix (10), determining at least one second FAS indicator (12) from the sample matrix (10), wherein the at least one second FAS indicator (12) is different from the at least one first FAS indicator (11), and generating the FAS finding (30) using an indicator spectrum (20) comprising the at least one first FAS indicator (11) and the at least one second FAS indicator (12). The invention also relates to an analysis device (100) for providing a FAS finding (30) with a computer program product according to the invention (90) and a storage means (80) with a computer program product (90) according to the invention stored thereon.

The invention relates to methods of using variants of fibroblast growth factor 19 (FGF19) for treating primary biliary cirrhosis.

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

The invention relates to variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of FGF19 and/or FGF21, and variants or fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics), having one or more activities, such as bile acid homeostasis modulating activity, and methods for and uses in treatment of bile acid and other disorders.

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

Provided herein are thiazolidinedione analogues that are useful for treating non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), diabetes, and other metabolic inflammation-mediated disease and disorders. Further, provided herein are non-invasive methods and systems for assessing a subject's risk of having NASH. Moreover, provided herein are non-invasive methods and systems for evaluating whether a treatment of NASH is effective.

The present invention provides compositions and methods for the treatment or prevention of a lysosomal disease or disorder involving increasing the level, expression, or activity of a metallothionein polypeptide or polynucleotide in the subject.