At Baylor Research Institute (BRI), small medical wonders are moving from the laboratory to patient care. : :   A new application of an existing medicine has allowed many children once crippled with arthritis to now run and play. Other research has revealed that a medicine for osteoporosis could play an important new role in preventing breast cancer. : :   An innovative vaccine for melanoma created at BRI is showing promise in fighting skin cancer in more than 100 patients. Vaccines for other cancers also are being developed and tested. : :   And researchers are taking a new look at white blood cells by using a simple blood test that may uncover future health problems in patients before they experience any symptoms.

These are just a few of BRI's more than 650 active research projects in two dozen areas of medicine, from cardiovascular care to transplantation.

The institute is close to tripling its number of funded research projects since 2000, and it is continually attracting top-ranking researchers in their respective fields, says Michael A.E. Ramsay, MD, president of the research institute.

Much of this growth, Ramsay says, can be attributed to a strategic change six years ago in its guiding philosophy. BRI has developed a mission to conduct clinically relevant research that puts the focus squarely on moving important findings from the laboratory workbench to the patient's bedside, he explains.

"It separates us from most of the major academic research centers," says Ramsay. "We are supported by the health care industry, and to receive that support, our research has to improve the medical care of our patients and community."

William R. Duncan, PhD, chief operating officer and chief scientific officer at BRI, calls the institute a hybrid between academics, research and patient care.

"We're a hospital-based research institute — our success is due to our large patient base," he says. "We take a disease, go back to the lab to develop a treatment and then go back to the patient. Trying to advance patient care is the ultimate goal."

The 250 scientists, laboratory assistants and research coordinators that make up BRI seek to develop new strategies for the prevention and treatment of disease using novel approaches, for instance, the microbubble transportation of treatments to repair organs.

Other research studies focus on the evaluation of new drugs and therapies in clinical trials supported by the pharmaceutical industry.

Two years ago, the National Institutes of Health (NIH) made the goal of fast-tracking findings to bedside care — so-called translational research — a priority, Ramsay says.

"Our research has an ending that is not measured in years," he says, "so we can make a difference."

The 24-year-old institute had a strong track record of clinically significant research even before it gained its new momentum. Among that research:



Today, BRI continues on its path of pushing lab research to bedside application. For example, a number of studies are under way in the field of immunology.

In July, BRI was awarded a three-year, $3 million grant from the National Cancer Institute to continue its development of vaccines for the often deadly skin cancer melanoma. The grant will fund the seventh such clinical trial led by Jacques Banchereau, PhD, director of Institute for Immunology Research, building off very promising earlier trials.

The vaccine uses the patient's own special immune system cells, known as dendritic cells, to attack the cancer and destroy it. During the past six years, more than 500 individual vaccines have been manufactured and used to treat more than 100 patients with late-stage metastatic melanoma.

In 2004, Baylor Health Care System formed its first biotech company, called ODC Therapy Inc., to develop and produce customized cancer vaccines.

One trial, described by Banchereau and colleagues in the September/October 2005 issue of the Journal of Immunotherapy, tested the vaccine therapy on 20 patients with stage IV melanoma. At the end of the study, four of the patients had survived between two years and more than three years after the vaccine therapy began.

"We've only used the vaccine after every other therapy has been tried," says Ramsay. "Patients in the trial are dying of the cancer."

Plans are under way to use the vaccine therapy in patients with less advanced cancer, in combination with other therapies, Ramsay says, to "construct a therapy to control the disease."

BRI also is working to develop a therapeutic vaccine for non- small cell lung cancer, which accounts for the vast majority of lung cancer cases.

While these vaccines are being used as therapies, other vaccines being developed at BRI are aimed at preventing viruses that lead to cancer. In its 40,000-square-foot laboratory, the Baylor Institute for Immunology Research houses more than 100 researchers, many looking at these vaccines.

"They've been able to harness the immune system and find antibodies that can block these viruses," Ramsay says.

Two grants from the NIH will help support research into the prospect of a viral-prevention strategy using vaccines to head off colon cancer. And similar work will begin next year on a preventive strategy with vaccines against prostate cancer.


Another immunologic study by Banchereau and Virginia Pascual, MD, successfully treated children with systemic onset juvenile idiopathic arthritis, or SoJIA. The disease accounts for between 10 percent and 20 percent of the 250,000 cases of juvenile arthritis in the U.S.

In the trial, researchers at BRI determined that an immune system protein, interleukin-1, is overproduced in children with SoJIA. They then found that the drug Anakinra^® (which was already on the market to treat rheumatoid arthritis) could block the effects of this protein on the body. Findings of the trial were published in May 2005 in Journal of Experimental Medicine.

By receiving a daily shot of the drug, the children with SoJIA in the trial were relieved of arthritic symptoms in their joints within a few weeks. The drug also has improved the patients' white blood cell counts and other symptoms of arthritis. Six of the eight children in one trial had function fully restored by the therapy, and the other two had lessened symptoms, Pascual says.

"Changes can be spectacular," she says. "We have children who went from a wheelchair to walking and jumping."

Several trials are now being conducted with larger groups of children.

That same approach of finding immune system irregularities and applying medications to address those issues is being used to evaluate new biologic drugs for the treatment of psoriasis and psoriatic arthritis, Ramsay notes. In another related area, BRI announced in November that it will be establishing a Center for Lupus Research using a highly competitive $6.2 million grant from the NIH. The research institute will focus on discovering exactly what triggers lupus, which affects 1.5 million Americans. From that research, the institute will measure responses to therapies that attempt to address that triggering mechanism.

"Research will be focused on controlling it, not curing it," Ramsay says.

BRI also is putting new emphasis on medical issues that affect the nation's aging population. This effort includes a clinical trial using adult stem cells to rejuvenate damaged heart muscle in patients with severe congestive heart failure.


In the autoimmunity program, researchers are looking at white cells in a blood sample to identify the specific signature of bacterial viruses — which could enable doctors to identify patients' risk of illness before they experience actual symptoms, Ramsay says.

"This research allows us to obtain the fingerprints of disease," he says.

Ramsay says pharmaceutical companies are coming to BRI to support development of this diagnostic tool. The recently revealed heart-related side effects of some widely used arthritis drugs, for example, might not have occurred if doctors could more precisely identify which patients would be hurt by the drug. Other uses could be to rapidly identify the movement of potential pandemic diseases such as avian flu or SARS, Ramsay says.

"We are the leader of the pack in this [type of] research," he says. "And it's developing very fast."

With one of the largest liver transplantation programs in the country located at Baylor University Medical Center, transplantation research continues to be an important area for BRI, Duncan says.

A world leader in the field of islet cell transplantation research, Shinichi Matsumoto, MD, PhD, of Kyoto, Japan, recently joined BRI as it expanded its reach to Tarrant County.

Matsumoto is the first to have performed a successful islet cell transplantation from a living donor, Ramsay says. Such work with pancreatic islet cells is not only at the leading edge of transplantation, but has come onto the forefront of research in the treatment of type 1 diabetes.

In the Baylor Motion & Sports Performance Center in the Department of Orthopaedics, Fabian Pollo, PhD, director of orthopaedic research, and a team of researchers are using a high-resolution 12-camera system to create a three-dimensional skeletal representation of human motion. In one clinical study, Pollo is using the camera at the Baylor Motion & Sports Performance Center to look at the results of patients who have received total hip replacements using minimally invasive surgery. The cameras also are being used to analyze the way people walk before a joint is replaced, Ramsay says.

"The research helps orthopaedic experts on the medical staff at Baylor design new artificial joints based on the way the original joints move," he says. "It makes the joints more customized."

In addition to research on medications, medical procedures, and disease prevention, BRI has active research programs aimed at improving community health and health care.

Project Access is looking at addressing health needs of the community to increase availability of primary care to patients who need it most. This study included more than 270 subjects living in 12 targeted zip codes in central Dallas who are uninsured, have low income and had visited the ER more than twice in the preceding year. One outcome of that project has been the creation of a community-based chronic disease management program for patients with diabetes at Central Dallas Ministries' Community Health Services.

A BRI study sponsored by the American Diabetes Association examined the effectiveness of practice-based diabetes resource nurses working with physicians to improve patient care. Another BRI study looks at reducing use of antibiotics in babies in the neonatal intensive care unit.

Next year, Robert Mayberry, PhD, who recently joined Baylor as director of health disparities research and director of the section of epidemiology, will be looking at disparities in the U.S. health care system, Ramsay says.

"We have a sick-care system, not a health care system," he says. "We treat the sick, not the healthy."

Yet early diagnosis can allow a patient to be treated with minimal expense and hardship, he points out.

"By investing in health instead of sick care, we can have a much healthier society."  : :

• To find a clinical trial that may interest you, call 1-800-4BAYLOR
• More about fighting cancer with vaccines
• Details about the treatment study for systemic onset juvenile idiopathic arthritis
• Islet cell transplantation
• General information about Baylor Research Institute