Through Technologies

New Inventions

Treating Hemophilia B with Modified Protein

A UW–Madison researcher has developed new Factor IX mutants for treating blood coagulation conditions, including hemophilia B, hemorrhagic disorder and thrombosis. The modified proteins contain combined mutations in the heparin and antithrombin binding sites that prolong half-life and stability.

The new mutants show improved in vivo activity and more sustained therapeutic effect than naturally occurring Factor IX. They could potentially be administered intravenously, orally or by another route.
(Oct 30, 2015) P150063US02

Treating Iron Overload with Block Copolymers

UW–Madison researchers have developed new block copolymers for forming micelles that can respond to the oxidation state of their environment and chelate iron (II) and (III) ions. At suitable concentrations the copolymers can form micelles to prolong circulation in the blood and bind to non-transferrin bound iron. The micelles then break up in cells in the presence of oxidizing agents such as hydrogen peroxide and are cleared from the body by the liver or kidney route.

The copolymers include a polyhydroxamic acid-containing block and a polyferrocenyl block. They can be prepared by standard peptide synthesis or polymerization methods.
(Oct 6, 2015) P140395US02

Modified Yeast with Enhanced Tolerance for GVL Biomass Solvent

UW–Madison researchers have developed a genetically modified strain of Saccharomyces cerevisiae that is more resistant to GVL toxicity and grows more than 1.5 times faster than wild yeast in the presence of GVL.

The researchers deleted two genes (Pad1p and Fdc1p) in the yeast that play a role in mediating GVL tolerance. The new strain is the first ethanol-producing yeast specifically tailored for GVL-based techniques.
(Sep 9, 2015) P140430US02

Sustainable Process to Remediate Liquid Waste Streams

UW–Madison researchers have developed an environmentally sound and cost-effective system to remediate effluent streams containing organometallic/inorganometallic contaminants. Metals are recovered in the process and the treated water can be recycled for industrial applications.

The system includes units for electro-oxidation, electro-deposition and electro-adsorption. These units work sequentially to (1) break the strong chemical bonds in the waste stream, (2) recover the heavy metal ions and (3) remediate the organic/inorganic material.

A primary advantage of the new system is the redesigned electro-deposition unit, which houses a concentrating cathode and helps in the recovery of metals present even in very low concentrations in a reusable form.
(Aug 6, 2015) P140335US02

Synthesizing Natural Products to Treat High Blood Cholesterol

UW–Madison researchers have developed an efficient method to synthesize indole compounds, specifically polysubstituted dimeric indoles. These compounds have potential health benefits because they are able to reduce the amount of PCSK9 in cells. PCSK9 is an enzyme known to play a major role in controlling the concentration of LDL cholesterol in the bloodstream.

Some of the compounds have been tested in vitro for their ability to increase the secretion of a potent blood sugar hormone in the body called glucagon-like peptide 1 (GLP-1). Others have the ability to selectively inhibit the secretion of interleukin-17 (IL-17), which is essential in many autoimmune diseases including arthritis, multiple sclerosis, psoriasis and inflammatory bowel disease.

The synthesis process involves a cascade reaction with transition metal catalysts. The resulting compounds can be further functionalized to yield more substituted indoles.
(Aug 5, 2015) P150023US03

New Broad-Spectrum Antibiotics

A UW–Madison researcher and collaborators have identified an antibiotic compound effective against many drug-resistant, Gram-negative and Gram-positive bacteria. The compound (5-nonyloxytryptamine) and its analogs are small molecule inhibitors that interfere with the bacterial membrane and prevent replication.

The compound has been reported as an anticancer drug but was not previously shown to have antimicrobial properties. It was identified by searching for compounds that cause E. coli bacteria to lack a copy of the chromosome following cell division.
(Jul 2, 2015) P140321US02

Generic Drug to Treat and Prevent Macular Degenerative Diseases

UW–Madison researchers have identified a new treatment option for a number of macular degenerative diseases including AMD, Stargardt’s disease and juvenile macular dystrophy.

The researchers found that a class of compounds called acid sphingomyelinase inhibitors can be used to fight retinal disorders associated with abnormal accumulations of lipofuscin (a cellular waste product), cholesterol or increased inflammation. One such inhibitor, generic name desipramine, is currently sold on the market as an antidepressant. Other acid sphingomyelinase inhibitors also may be suitable.
(Jun 22, 2015) P140282US02

More Potent UGM Inhibitors for Treating Tuberculosis and Other Microbial Infections

UW–Madison researchers and collaborators have identified a potent set of UGM inhibitors that may help fight tuberculosis and other diseases caused by microbial infections. The compounds contain a bicyclic triazolo thiadiazine core with diversified aromatic substituents. They were identified by virtually screening a database of nearly five million commercially available compounds.

The molecules inhibit the growth of microorganisms that depend on UGM to incorporate Galf residues. They also diminish the virulence of pathogenic microorganisms, such as M. tuberculosis, M. smegmatis and Klebsiella pneumonia, that rely on UGM.
(Jun 2, 2015) P140379US02

Treating Absence Epilepsy with Ganaxolone

UW–Madison researchers have developed a method for treating absence epilepsy with the drug ganaxolone, a synthetic neurosteroid analog that modulates GABAA receptors. The drug has shown promise for treating other forms of epilepsy but has not been recommended for absence epilepsy until now.

The researchers have found that in low doses the drug provides an optimal amount of tonic inhibition that restores function and reduces symptoms in a mouse model. The drug may be particularly useful for treating young patients whose condition is characterized by a reduction in tonic inhibition.
(May 21, 2015) P140051US02

Combination Therapy Kills Cancer Cells

UW–Madison researchers have developed a new cancer treatment that combines a TRAIL receptor agonist with the diabetes drug metformin. Metformin sensitizes even resistant cancer cells to the TRAIL receptor agonists (e.g., lexatumumab) that induce cell death.

Metformin is attractive because its safety has been established over decades in diabetic patients worldwide. As such, there seem to be few barriers to its clinical implementation as a cancer therapeutic in combination with TRAIL receptor agonists. Metformin is commercially available as Glucophage® or in generic form.
(Apr 21, 2015) P140221US02