A new St. Louis-based company will use a novel technology to rapidly screen thousands of drugs for their effectiveness against two of the biggest health threats in the United States — diabetes and cancer.
Ross Cagan, Ph.D., professor of molecular biology and pharmacology at Washington University School of Medicine in St. Louis and Thomas Baranski, M.D., Ph.D., professor of medicine, will head the new company, Medros Inc. The company's technology can identify drugs with medical benefit by capitalizing on extensive information currently available about fruit fly biology and genetics.
Launched with the joint backing of the School of Medicine and BioGenerator, a nonprofit group formed to help spawn biotech companies from university research, Medros will soon begin operation in the Center for Emerging Technologies.
The company arose from a collaboration between Cagan and Baranski, who is also an endocrinologist at Barnes-Jewish Hospital. Cagan showed Baranski a method developed in his lab for determining if a drug could correct abnormal development in the eyes of fruit flies. Impressed with the concept, Baranski asked if it could be adapted to screen for drugs that could alleviate the complications of diabetes.
"People with diabetes can go blind, their kidneys can fail and their nerves can die," says Baranski. "We don't have any good drugs for counteracting these effects. We know that high blood sugar contributes to these problems, so I went to Ross and asked if his fruit fly system could uncover why high glucose can be toxic."
This challenge led to a full-fledged screening system in which fruit flies, grown from eggs to adults in tiny chambers, serve as indicators of a drug's effect. In this instance, if a fruit fly can grow normally on a high sugar diet in the presence of a particular drug, the drug could potentially lessen the toxicity of high sugar in diabetics, according to Baranski.
Using fruit flies for drug screening is fast and inexpensive because the flies' short life spans and small size allow quick turnaround and multiple simultaneous tests in a small space. Furthermore, the technique determines a drug's effect on the whole organism, not on isolated cells.
"If you start the process of screening drugs by looking at cells in a dish, you miss the effect of drugs on the molecular pathways involved in the whole organism," Cagan says. "For example, metastasis of cancer is actually a response to normal tissue sending a signal to tumor cells telling them to leave the tumor. If you study cancer in a dish, you can't look at that process at all. For decades, researchers have studied cancer this way because it's easy. But that hasn't resulted in significant progress toward a cure."
Cagan and Baranski have developed their screening method to identify drugs effective against metastatic cancer. A simple change in the appearance of specially engineered fruit flies can indicate that a drug may prevent metastasis.
The researchers are confident that their fruit fly model parallels human physiology to a great extent. Molecular pathways that play a role in diabetes and cancer are present in both humans and fruit flies, according to Cagan.
In addition, the researchers feel their approach may be superior to more traditional approaches that go after one disease target, such as a chemotherapeutic drug that aims to influence one gene responsible for cancerous growth.
"With our method, we aren't asking what the target is — we're letting the system tell us," Cagan says. "We're just asking for the bottom line. Do the flies get better? If you find the magic compound that hits everything that contributes to the disease in just the right amount so that the fly can live, then you've made true progress."
Medros gives the researchers a mechanism to obtain private drug libraries, establish the effectiveness of their technology and potentially attract commercial interest to their discoveries.
"We believe in the technology," Baranski says. "But we're scientists, not businessmen. That's where BioGenerator came in. They were willing to invest in us, and together with the Office of Technology Management here at Washington University, they were able to help us through the fairly involved process of creating a company."