The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

Methods for treating Cushing's Syndrome and other conditions associated with excessive cortisol production such as Cushing's Disease, ectopic adrenocorticotropic hormone secretion, ectopic corticotropin-releasing hormone secretion, adrenal-dependent Cushing's Syndrome, adrenal adenoma, adrenal autonomy, or any other condition associated with persistent or recurrent endogenous hypercortisolemia are provided. The methods include administration of a 2S,4R ketoconazole enantiomer substantially free of the 2R,4S enantiomer to patients according to a dosing titration schedule or at an effective amount. Treatment methods according to the invention may be safer and more effective than treatment using racemic ketoconazole.

The instant disclosure relates to methods and compositions for the treatment of Gaucher disease, particularly type II and III neuronopathic Gaucher disease (nGD). The methods include the step of administering to an individual in need thereof an effective amount of a ryanodine receptor inhibitor or a pharmaceutically acceptable salt thereof.

The invention provides methods of treatment that induce satiety in a subject for a period of at least around twenty-four hours by once-daily administration to the subject of a controlled release dosage form, wherein the dosage form is administered while the subject is in the fasted state and at a time of around six to around nine hours prior to the subject's next intended meal, and wherein the dosage form comprises a controlled release composition, which comprises an enterically-coated, ileum hormone-stimulating amount of a nutritional substance and releases the majority of the nutritional substance in vivo upon reaching the subject's ileum. The invention also provides a diagnostic tool for probing the health and disease state of the ileal hormones, excess or deficiencies. The invention provides a safe vehicle for targeted deliveries of chemical, pharmaceuticals, natural substances and nutrition to the ileum. The present invention also provides a method for treating noninsulin dependent diabetes mellitus, pre-diabetic symptoms, and insulin resistance, as well as a number of disease states and conditions including gastrointestinal disorders as otherwise described herein.

The present invention is related to a method for diagnosing Farber's disease in a subject, wherein the method comprises detecting C26 ceramide in a sample from the subject.

The present disclosure provides methods, systems, compositions, and kits to address the need for microbiome-related treatment of health conditions and disease. The present disclosure provides for treatment of metabolic conditions using microbial compositions.

The invention relates to in vivo systems and high throughput screening platform for drugs applicable in inborn error of metabolism (IEM) disorders. More specifically, the invention provides yeast screening system of candidate therapeutic compounds applicable in IEM disorders associated with accumulation of at least one metabolite. The systems of the invention comprise yeast cell/s that carry at least one manipulation in at least one yeast metabolic pathway, that leads to accumulation of said metabolite.

Described herein is a novel, mitochondrial encoded, open reading frame, that leads to the production of a new mitochondrial peptide. Residing within the ND-Two subunit, a specific small nucleotide polymorphism disrupts expression of this mitochondrial peptide, and is correlated with an increase in obesity and diabetes, particularly in certain ethnic populations. In vitro administration of the peptide increases insulin secretion, decreases fat accumulation and improves glucose uptake in muscle cell. Antibodies generated against the peptide can be used for detecting peptide deficiency, in addition to SNP detection, supporting diagnostic approaches. In vivo studies further revealed that administration of the peptide improves glucose tolerance, thereby providing a new therapeutic avenue for a novel diabetes therapy and decreases bodyweight, thus serving as a novel obesity therapy. Generation of synthetic analogs further enhance or abrogated activity relative to the natural peptide.

This disclosure is directed to methods of methods of computing a composite measurement comprising employing two or more sub-instruments to measure one or more clinical symptoms of mitochondrial dysfunction or mitochondrial disease. This disclosure is also directed to methods of assessing and managing a subject with mitochondrial dysfunction or mitochondrial disease using a composite measurement.

Methods of using biomarkers in determining the efficacy of a treatment for an organic acidemia in a subject are disclosed herein. Methods of using biomarkers in determining the efficacy of a liver-directed treatment for an organic acidemia in a subject are likewise disclosed herein.