University of Wisconsin–Milwaukee

 

A four-year partnership between a University of Wisconsin–Milwaukee chemistry lab and researchers at UW–La Crosse has yielded several potential new antibiotics to fight bacteria that cause staph infections, anthrax, tuberculosis and other infectious diseases.

The lab of James Cook, UWM Distinguished Professor of Chemistry, provides the key medicinal chemistry necessary for designing new drugs from a brand-new class of anti-infective agents discovered by UW–La Crosse researchers Aaron Monte, professor of chemistry, and William Schwan and Marc Rott, professors of microbiology.

These agents are derived from a shrub that has been used as an herbal remedy by the Ojibwe.

“Because this is a new structural class of compounds, we can continue to manipulate parts of the core structure, with the goal of creating additional drugs that may be more potent and effective,” says Monte.

One of the drug candidates synthesized by Cook’s lab is effective against at least 20 “gram-positive” bacteria – those with thick cell walls that are resistant to existing broad-spectrum antibiotics.

Two other compounds from this class are effective against tuberculosis. In fact, both surpass the potency of the existing drug, Rifampin, in treating the disease, says Cook’s doctoral student M. Shahjahan Kabir, who with Ranjit Verma has synthesized the key compound for development.

The group has two joint patents pending on the work, both through the WiSys Technology Foundation Inc., an independent foundation chartered to support research at UW System campuses other than Madison.

Now the team is looking for funding to take the lead drug candidate, called SK-03-92, into preclinical trials.

Because bacteria tend to become resistant to often-prescribed antibiotics eventually, the need for new ones is constant, though fewer are being developed.

“Unfortunately, due mainly to a lack of profit motive, big pharmaceutical corporations have shied away from doing this sort of research for decades, and we are now in a state of crisis,” says Monte.

More collaborations like this one can help, says Cook. In fact, the partnership has become the model for UW System-sponsored intercampus research through the Wisconsin Applied Research Program (WARP). The WARP, which was a funding source for the Monte-Cook collaboration, is designed to encourage faculty to apply their scholarship to support economic development in Wisconsin by offering one-year support of up to $50,000.

“Because of this collaboration, we have been able to develop and tie in brand-new chemistry with drug design, which is a real goal here,” says Cook.

Cook and the UW–La Crosse researchers both conduct drug discovery research from natural products.

Cook holds 16 patents and two pending through WiSys, and also four patents pending through the UWM Research Foundation. His intellectual property, which involves compounds to treat diseases from schizophrenia to alcoholism, has been licensed by three startup companies in Milwaukee.

In 2005 Monte and Rott formed a startup company, Mycophyte Discovery LCC, with Schwan and Thomas Volk, UW–La Crosse professor of biology. The company aims to develop drugs, particularly new antibiotics, from plants and mushrooms.

A bill being considered by the state legislature this session would provide some funding to create an Emerging Technology Center in Pharmaceutical Development, a collaborative facility headquartered at UW–La Crosse, that would investigate new drug discovery from natural products. UW–La Crosse would have to match the funding if the bill is approved.

But the partners have already lined up: In addition to Cook’s lab, researchers from UW–Madison’s School of Medicine and Public Health, and School of Pharmacy; the UW Small Molecule Screening Facility; UW–Eau Claire; UW–Platteville; and three institutions in other states would be involved. The collaboration would also work with the Marshfield Clinic, Gundersen Lutheran Medical Center and the Ojibwe and Ho Chunk nations.