Pharmaceuticals & Vitamin D : Metabolic disorders

Pharmaceuticals & Vitamin D Portfolios


Vitamin D Analogs 2MD and 2AMD Prevent Type 1 Diabetes without Inducing Hypercalcemia

UW–Madison researchers have identified vitamin D analogs that can prevent type 1 diabetes in the NOD mouse at doses that do not induce hypercalcemia. The vitamin D compounds are 2α-methyl-19-nor-20(S)-1,25-dihydroxyvitamin D3, known as 2AMD, and 2-methylene-19-nor-20(S)-1,25-dihydroxyvitamin D3, known as 2MD.

Glycomacropeptide (GMP)-Based Food for the Treatment of PKU and Other Metabolic Disorders

UW-Madison researchers have developed an improved medical food for treating PKU.  This food is made with highly purified glycomacropeptide (GMP) as its primary protein source and supplemented with other amino acids, including arginine, histidine, leucine, tyrosine and tryptophan.  It provides a complete, low-phenylalanine source of protein and is more palatable than the standard specialized diet.

GMP is a naturally occurring protein that is formed during cheese making and contains no phenylalanine.  The purity of GMP is one key to producing this medical food.  The other is the amount and type of amino acid supplementation.  For example, if too many sulfur-containing amino acids are used, the food tastes bad and patients will not eat it.

A New Phosphate Binder for Blocking Phosphate Absorption and Reducing Hyperphosphatemia

UW-Madison researchers have developed compositions that reduce phosphate absorption in the intestine. These compositions could be administered to patients to lower blood phosphate levels, decreasing the risk of developing renal osteodystrophy.

The compositions consist of dendrimers, which are highly branched, symmetric molecules. Dendrimers are well known therapeutic tools, although dendrimers that bind phosphate were not known previously. The dendrimer compositions of this invention may include a hydrochloride, hydrobromide, hydroacetate or other hydroanionic form. 

αKG Analogs Increase Glucose-Induced Insulin Secretion, Provide Method of Treating Hyperglycemia in Type II Diabetics

UW-Madison researchers have developed a method to increase glucose-dependent insulin secretion. They discovered that an analog of alpha-ketoglutarate (alphaKG), which can be converted into the insulin secretagogue succinate, increases glucose-induced insulin secretion both in vitro and in animals, particularly in humans and rodents. AlphaKG analogs directly regulate the activity of ATP-sensitive potassium ion channels (KATP) and enhance the glucose-dependent regulation of KATP, leading to greater insulin secretion at high glucose concentrations than at low concentrations. An alphaKG analog could be administered to an individual with Type II diabetes to treat hyperglycemia (high blood sugar).

Method for Preventing Superoxide Damage to Cells and Oxygen-Labile Proteins

UW-Madison researchers have developed a method of protecting cells and oxygen-labile enzymes from oxidative damage. YggX is a protein identified from Salmonella enterica serovar Typhimurium. Elevated levels of the YggX protein increase the resistance of Salmonella enterica to superoxide stress and reduce damage to its DNA. Also, when high levels of this protein are present in the cell, enzymes that are normally susceptible to oxidative damage remain active. Engineering cells to overexpress the YggX protein or its homolog renders the cells more resistant to oxidative damage. The YggX protein or its homolog could also be used to protect an oxygen-labile protein from superoxide damage by co-expressing YggX with the oxygen-labile protein.

Compounds to Treat Hyperlipidemia and Fatty Liver Disease

UW–Madison researchers and collaborators have developed compounds that can be used to prevent fatty liver disease resulting from MTP inhibitors. The compounds selectively inhibit the liver-specific isoform of fatty acid binding protein (L-FABP). Suppression of L-FABP activity has been shown to block the fatty liver side effect caused by MTP inhibitors without diminishing the latter’s lipid-lowering benefits.