Moving Medicine Forward

Bacteria are commonly blamed for infections, but, actually, it’s often the toxins bacteria secrete that cause serious problems. Recently, microbiologist Patrick Schlievert discovered a compound that prevents bacteria from producing toxins—like those produced in toxic shock syndrome.

By Brenda Hudson

Almost immediately, Schlievert began to wonder about the potential medical applications of the discovery.

 “That’s the whole point about medical research,” says Schlievert. “As researchers, our focus should be on disease and what we can do about it.”

Schlievert found that the compound glycerol monolaurate, known as GML, may play an important role in treating and even preventing bacterial and viral infections, such as staphylococcal toxic shock syndrome. “In the presence of GML, viruses and toxins can’t be taken up by host cells,” explains Schlievert. “It also kills many bacterial organisms.”

Found naturally in breast milk, GML also may effectively fight bioterrorism agents such as anthrax or perhaps slow the effects of aging. Based on the initial findings, Schlievert now is working with University physicians on a range of clinical trials with patients. They are testing whether GML-treated tampons and GML gel formulations will prevent bacterial infections, yeast infections, and the potentially fatal toxic shock syndrome. If results are positive, the University, which has patent applications in these areas, hopes to partner with industry to provide safe, effective products to the public.

Schlievert is just one of many University scientists whose discoveries fuel clinical research. From a variety of disciplines, these scientists work toward new treatments and better understanding of diseases and conditions, including diabetes, cancer, heart disease, and brain and nervous system disorders, as well as animal health and food safety.

The University supports such a scope of research activities because the benefits of clinical research are so great, says Jasjit S. Ahluwalia, executive director of the Academic Health Center Office of Clinical Research, which opened in September 2005. “The focus of clinical research is to improve the lives of people,” he says, “to help them not only live longer, but also live better, healthier lives. We’re working to eradicate childhood illness, to cure diseases— and even better—to prevent disease and promote health.”

Ahluwalia is leading a number of initiatives to increase the value and quality of clinical research at the University. His goals are to foster collaboration between investigators working in different disciplines, to engage in community partnerships that address key health care issues, and to help researchers obtain grant funding as well as to more effectively and efficiently conduct their research. Ahluwalia recognizes that collaboration is essential to meeting these goals, so he has enlisted a multidisciplinary task force to drive the changes necessary to further clinical research. “We’re very committed to improving the breadth and value of clinical research at the University,” he says. “We’re also very aware of why we’re doing this—to ultimately improve our community’s health.”

In addition to clinical trials, clinical research Includes epidemiologic research, which examines how often diseases occur in different groups of people and why. School of Public Health epidemiologist Beth Virnig is looking at the health effects of cancer care treatments to help determine best modes of treatment. “Radiation is often given as a treatment for cancer,” she says. “Unfortunately, it can also damage other, healthy cells, sometimes resulting in subsequent cancers or other health problems.” The question for Virnig is: What are the risks posed by radiation treatments? Because radiation is the standard of care for treating many types of cancer, it would be unethical to submit patients to randomized clinical trials during which they may be denied standard of care in order to investigate a research question.

Fortunately, Virnig found a way around this. By analyzing Medicare and cancer registry data for patients who did and did not undergo radiation treatment and by tracking their health after radiation treatment, she was able to determine some of the risks faced by cancer survivors. For instance, she found that patients receiving radiation for cervical cancer were more likely to experience a pelvic or hip fracture.

Using these findings, Virnig is working with gynecologic oncologist Levi Downs to inform patients and their health care providers of potential health risks.

“The information gained from this type of research, is useful to me as a physician caring for patients,” Downs says. “It can help inform treatment. For instance, for those who have received radiation for cervical cancer, we now know to provide treatment that can help prevent bone fractures.”

Outside of clinics and labs, clinical research can also occur in the community. School of Nursing professor Cheryl Robertson is helping Somali and Oromo refugee women living in the Twin Cities adapt their parenting skills to their new environment. “These women are accustomed to parenting in a close-knit community with extended family support,” says Robertson. Living here, the women may feel isolated and unsure how best to parent their children, she adds. Supported by a grant from the National Institutes of Health, Robertson and fellow nursing professor Linda Halcon are assessing the feasibility and acceptability of an intervention known as “health realization.”

Working with several community groups, Robertson helps the women reconnect with the community and problem-solve with each other. “These women are hungry to re-learn how to tap into their own strengths so they can arrive at their own decisions on how to handle situations with their children,” says Robertson. “We hope the result will be happier, healthier families.”

Clinical research also may involve testing new drugs or medical devices. This type of research usually requires submission of an investigational new drug (IND) application or an investigational device exemption (IDE) application to the U.S. Food and Drug Administration—a notoriously complicated process. “Complying with the FDA’s regulations can be daunting to faculty researchers,” says Mark Paller, AHC assistant vice president for research.

Recognizing this, the AHC created an assistance program to help investigators navigate the application process. Program director Harvey Arbit, who has more than 30 years experience in this area, offers his expertise to investigators, “enabling them to concentrate more on the science and less on the paperwork.” He also educates them on their obligations to the FDA, helping ensure they meet regulatory requirements.

School of Dentistry resident Casey Turner says Arbit was a “savior” in helping her apply for an IND application. Interested in relieving post-operative endodontic pain following procedures such as root canals, Turner wants to use a non-steroidal anti-inflammatory drug in a new way, which requires FDA approval. “We want to see whether administering this drug intranasally will bring faster relief” than the standard of care, such as ibuprofen given as a tablet. Although confident about the science of her proposed study, Turner says, “I didn’t have a clue how to obtain FDA approval.” The IND assistance program “helped make sure I was on the right track” in meeting the FDA’s application requirements.

Turner also takes advantage of another service offered by the AHC to help streamline the research process. The clinical trials monitoring service helps researchers organize their data collection and documentation to meet the FDA’s Good Clinical Practice, a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials. Maintaining good records may not be the reason investigators enter the field, but it is a necessary component of research. Monitors Valerie O’Brien and Kathy Mischke insist they are not the research police. “Rather we offer assistance that will support researchers in monitoring and reporting how they perform clinical trials, and documenting any concerns,” says O’Brien.

Many clinical research studies conducted at the University use the General Clinical Research Center (GCRC), one of only 70 such centers nationwide. With funding of $19 million by the National Institutes of Health, the GCRC supports clinical researchers across the AHC, providing space, nursing support, and specialized services such as dietitians. The GCRC also helps support the Office of Clinical Research’s training mission.

The role of training and mentoring to promote clinical research is an area of particular interest to Ahluwalia, who wants to engage students as early as possible. “We’re reaching out to high school students and undergraduates, as well as graduates already in health sciences, to show them that a career in clinical research is extremely rewarding.” Ahluwalia is equally passionate that those who pursue a career in clinical research are provided with mentoring opportunities to help ensure their success in this competitive and challenging field. “It’s extremely rewarding to witness a researcher’s progress from tentative questioning to uncovering important answers—and even more rewarding to be a part of that development.”

“Supporting the next generation of clinical researchers is crucial,” agrees Paller. “If there were a lack of clinical researchers, we’d be frozen in time. There would be no medical progress.”

To help ensure progress in biomedical research, the Office of Clinical Research is expanding its training capabilities through a recent NIH grant. Led by School of Public Health professor Russell Luepker, the $13.8 million grant will foster multidisciplinary research throughout the AHC’s six health professional schools and support more than 20 up-and-coming researchers.

“The future for clinical research is extremely bright,” says Ahluwalia, “and this cannot help but translate into very real benefits for our patients, today and in the future.”