A factory for health advances

In a windowless fourth-floor lab high above the University of Colorado’s Folsom Field, postdoctoral research associate Brooke Harrison squints through a microscope at a pulsing cell from a rat heart. Nearby, a 6-foot-long Burmese python lies coiled in its cage.

What would happen if you bathed the heart of a mammal in the blood of a just-fed python?

This seemingly obscure question has driven Harrison’s research for months, as he and colleagues in the lab of biology professor Leslie Leinwand work to unravel the mysteries behind the python’s unique physiology in hopes of developing better drugs for human heart disease.

“It won’t be next year or the year after, but I think it could happen within five,” said Harrison. “You always want the work that you do to end up helping people. But it takes time.”

Harrison is among the thousands of biomedical researchers patiently hunkering down each day in lab coats in academic research centers across the state, working on projects that could ultimately save or improve lives. According to the Colorado BioScience Association, the state’s research institutions spin off 20 new bioscience companies annually, fueling a growing local industry that employs 20,000 people across 600 companies. In FY 2010-2011 alone, CU’s glistening new Anschutz Medical Campus in Aurora drew $248.5 million in research funding from the U.S. Department of Health and Human Services. Across CU’s four campuses, biomedical research led to 176 new patent filings that year. Combined with the millions of research dollars flowing into labs at Colorado State University and elsewhere, that funding has helped turn the state into a factory for health advancement, with biologists, engineers, chemists, and clinicians collaborating to churn out everything from new cancer drugs to better joint replacement materials to novel painkillers.

“We have become much more known for this type of research,” said Sue James, PhD, who founded CSU’s School of Biomedical Engineering in 2005 to serve as a “nexus of biomedical researchers” from her campus and beyond. “Colorado is attracting some of the greatest minds in this area.”

Bio-Band-Aids and lifelike
cartilage from CSU

It was nearly 19 years ago in a CSU lab that James, an engineer with a doctorate in polymers from the Massachusetts Institute of Technology, set out to develop a material that would make artificial joints work better and last longer.

Nationwide, according to the American Academy of Orthopaedic Surgeons, roughly 229,000 people have hip replacements annually while 497,000 have knee replacements – numbers that are expected to double as active Baby Boomers succumb earlier to joint degeneration. The problem: Those artificial joints wear out in 10 or 20 years, meaning patients must wait as long as possible for surgery, or expect they will have a second one.

Two decades of chemistry experiments and mechanical testing by James and her graduate students has now yielded a new plastic that better mimics human cartilage and that wears 40 percent less after five years, according to simulations.

“We basically took this hard plastic that they use to make these implants out of and we gave it a snotty, lubricious surface,” said James.

In 2010, James teamed up with Indiana-based Schwartz Biomedical to license the technology, called Bio-Poly. And in January, two knee-resurfacing patients walked out of a London hospital with the first partial implants made with her technology. In the future, she sees it being used not only for total joint replacements but also for artificial cardiovascular tissue.

“It’s very exciting,” James said. “It’s been a long time coming.”

Melissa Reynolds may also see her brainchild lead to better patient care in the coming years. In March 2011, the CSU chemistry professor received a $1.3 million grant from the Department of Defense to expedite her work developing a wound-healing material for use on battlefields and the sites of natural disasters.

With the help of 19 undergrads and seven grad students, she developed a novel nitric-oxide infused bandage that aims to boost the body’s infection-fighting ability and promote healing. It could be placed on deep cuts on the skin or over deeper internal wounds and would absorb into the body over time. Her team has also filed for a patent and founded a start-up company to commercialize it.

“We could package them in water-safe bags and drop them from planes so people could apply them to the wound right away,” she said, noting that the technology would have been ideal for situations like the 2010 Haiti earthquake or 2011 Japan tsunami.

Personalized cancer care
at Anschutz

While CU’s Anschutz Medical Campus has been a mecca for biomedical research in many areas, it is gaining particular fame for its role in helping develop a new, more personal approach to treating cancer, one in which doctors screen patients for specific genetic drivers or “oncogenes” that fuel different cancer subtypes, then use molecularly targeted drugs to inhibit them.

For instance, instead of giving everyone the same treatment for lung cancer, drug choice can now be based, to a degree, on the type of lung cancer a patient has.

“We now know that what is driving the cancer is different between different cancers. If we can screen people for these oncogenic drivers and give them the right drug to interfere with the one they have, we can have a real impact,” said Dr. Ross Camidge, MD, director of the Thoracic Oncology Clinical Program at the CU Cancer Center at Anschutz Medical Campus. “One-size-fits-all treatments are yesterday’s paradigm. This is personalized medicine.”

A prime example is the drug Crizotnib, which gained Food and Drug Administration approval in August, based in part on CU-led research. The yellow pill works by inhibiting an oncogene called anaplastic lymphoma kinase (ALK), believed to turn healthy cells into cancer cells in roughly 4 percent of lung cancer patients. Only those who have the ALK mutation are eligible for the drug, but for them it has been remarkably effective. One trial Camidge led showed that of 82 patients treated with Crizotnib for six months, 47 saw their tumors shrink or disappear and 27 stabilized. All this in a disease for which the gold standard of treatment has long consisted of, as Camidge put it, “chemotherapy, more chemotherapy, and then hospice.”

The Crizotnib success story has paved the way for studies of other similar drugs, and scientists in various CU departments are now collaborating to make them happen.

CU cytogeneticist Marileila Garcia, PhD, who developed one of the world’s first screening tests for ALK mutations, is now working on tests for others.

The CU-led Lung Cancer Mutation Consortium has identified 10 other oncogenes for lung cancer, and is working to develop drugs for them.

And local clinical trials are showing promise for similar drugs for other cancers.

In February, CU cancer specialist Karl Lewis, M.D., co-wrote a report in the New England Journal of Medicine on Vemurafenib, a new oncogene-targeting drug for metastatic melanoma patients. It showed that 50 percent of patients benefited from the drug, with cancer growth halting for nearly seven months.

“Rarely do we see results this dramatic,” said Lewis.

Snake oil for heart patients and a new home for researchers

CU-Boulder biology professor Leinwand first started studying Burmese pythons six years ago, after reading a paper suggesting that by looking at the extreme physiological responses of certain species (such as bears and squirrels that hibernate), humans might be able to come up with new ideas on how to treat human disease.

Pythons are known to fast for months, then gorge on animals bigger than they are. Once the python eats, its metabolism increases fortyfold, and its heart bulges by 60 percent before returning to normal.

By studying pythons right after they eat, Leinwand, Harrison, and their colleagues have learned several things: 1) the heart growth in a just-fed python looks a lot like the healthy heart growth in a trained athlete (not the unhealthy growth that can occur in people with high blood pressure); 2) the magic potion fueling that healthy heart growth is a combination of three fatty acids coursing through the snake’s blood; and 3) when that blood is injected into a rodent, its heart grows in a healthy way, too.

If that unique milky plasma could be replicated and patented (it has) and commercialized (through a company called Hiberna, also in the works), Leinwand believes it could lead to novel drugs for preventing or treating heart failure and other diseases.

“The problem with people with heart failure is that many of them can’t exercise enough to get much of that benefit,” she said. “This would help them get the cardiovascular benefits of exercise with the exercise.”

But snake oil is hardly Leinwand’s only focus.

She recently teamed up with Nobel Laureate Tom Cech to found the new CU-Boulder Biofrontiers Institute, an effort to bring together scientists from across multiple disciplines in the name of advancing human health.

This summer Leinwand will move her lab — snakes and all — to a new 330,000-square-foot, $160-million building on the Boulder campus, which the new institute will share with the Department of Chemical and Biological Engineering and the Division of Biochemistry.

By fall, 600 researchers — from tissue engineers to computer scientists to biochemists — will arrive daily to do their work.

“We are attracting people who really want to solve problems of human health, and we are hoping for many patents to come out of this,” said Leinwand, the new institute’s chief science officer. “We’re going to energize the biotech community across the state.”


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