Pharmaceuticals & Vitamin D : Metabolic disorders

Pharmaceuticals & Vitamin D Portfolios


New Hormone Analogs for Treating Hypoparathyroidism

UW–Madison researchers have developed backbone-modified analogs of PTH(1-34). The analogs exhibit advantageous properties; they are biased toward Gs activation/cAMP production relative to β arrestin recruitment.

The analogs were generated via an unconventional strategy in which the backbone of a natural PTHR-1 agonist was altered, rather than the side-chain complement. More specifically, selected α-amino acid residues were systemically replaced with either β-amino acid residues or with unnatural D-stereoisomer α-amino acid residues.

The researchers have shown that backbone-modification can rapidly identify potent agonists with divergent receptor-state selectivity patterns relative to a prototype peptide.

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. 

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.

Novel Small Molecule SIRT6 Activators/Inhibitors

UW–Madison researchers have developed three novel compounds (CL-5D, SW-055, SW-062) that activate SIRT6 in biochemical assays. Two other compounds (CL-5D-Me and SW-055-Me) are methyl esters that are not expected to be active in biochemical assays but are expected to be more cell permeable and act as prodrugs, becoming active upon ester hydrolysis in cells.