Bear Cub grants awarded

Washington University in St. Louis has awarded five Bear Cub fund grants totaling $190,000 to support innovative research that has shown commercial potential.

The fund, made up of endowment income and capital from private sources, is administered through the university’s Office of Technology Management and helps scientists further develop their technology.

The grants were awarded to:

  • Michael Holtzman, MD, the Selma and Herman Seldin Professor of Medicine;
  • Jim Janetka, PhD, research assistant professor of biochemistry and molecular biophysics;
  • Jerry Morrissey, PhD, research professor of anesthesiology;
  • David Piwnica-Worms, MD, PhD, professor of radiology; and
  • Samuel Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences.

Holtzman and his colleagues will evaluate the safety and effectiveness of a drug designed to block the production of mucus. In respiratory diseases like asthma, bronchitis and the flu, the body produces too much mucus, which interferes with breathing.

Holtzman and his colleagues have developed a small-molecule inhibitor of mucus production and will evaluate the compound in animal models of airway disease and infection and in human airway cells grown in the laboratory. These studies will lay the groundwork for testing the drug in clinical trials in patients.

Recurrent urinary tract infections (UTIs) are a common problem for many women. They are typically treated with antibiotics, which are not always effective, and the bacteria that cause UTIs can rapidly develop resistance to antibiotics.

As an alternative, Janetka has designed a new group of drugs called mannosides, derived from the natural sugar mannose which don’t kill the bacteria like antibiotics but prevent bacteria from binding to and entering the bladder cells where UTIs occur.

Excess sugars are usually directed to the kidney and bladder, where they are eliminated in the urine, and mannosides are excreted in the same way, making them ideal for treating and preventing chronic UTIs.

Janetka and co-workers will optimize and evaluate lead compounds in the laboratory and then in animal models in preparation for early-phase clinical trials in patients.

Morrissey and colleagues are developing rapid tests for the early detection of kidney cancer and to monitor patients for the recurrence of the disease and metastases. They had identified a pair of proteins excreted in the urine that have the potential to detect about 90 percent of all kidney cancers.

The research team will now validate the tests using monoclonal antibody-based assays in urine samples of patients who are known to have kidney cancer, and compare their results to those in patients with non-cancerous kidney diseases and in healthy patients.

Radiotracer perfusion scans of the heart are often recommended for patients experiencing chest pain or a heart attack, so doctors can measure blood flow in the heart. But the medical isotope most commonly used today is in short supply.

Piwnica-Worms and his team have discovered a novel imaging agent that binds a new medical isotope, Gallium-68. He is evaluating whether the agent can noninvasively measure blood flow in the heart using high resolution PET scans.

Piwnica-Worms will further evaluate the imaging agent and the radiopharmaceutical in animal models, conduct toxicology tests and file an investigational drug application with the U.S. Food and Drug Administration so the agent can be evaluated in patients.

Wickline has developed a nanoparticle-based agent to inhibit and break apart blood clots that can develop suddenly, blocking blood flow to organs and tissues. This type of clotting typically is associated with heart attacks, strokes, bacterial toxins, acute kidney failure, drug reactions, sickle cell disease and sepsis.

Current treatments to control clotting often cause serious bleeding problems. The new nanoparticle agent under investigation is active specifically at the site where clots occur but does not inhibit normal clotting in other parts of the body, making bleeding problems less likely.

The agent binds only to acute clots and can be imaged to give an early noninvasive diagnosis of acute heart attacks and strokes in patients with suggestive symptoms. Wickline will continue to study the agent in animal models.