Date: Feb 19, 2011 Source: (
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A discovery made in the 1980s lead Kenneth Gruber to form the startup Tensive Controls in the hopes he can commercialize a drug that could help people with a wasting condition known as cachexia. The endeavor is like a second career for Gruber. "How do you want to be remembered? I thought I could cure a few diseases."
As a medical researcher working in North Carolina in the 1980s, Kenneth Gruber made a curious discovery.
He became aware that nearly every organism — from the lowliest mollusk to the most complicated human — has a strange on/off switch, a primordial control hidden deeply in DNA capable of influencing the cardiovascular system.
For the most part, the "switch" remains turned off, which is a good thing because humans suffer horrible side effects when it's activated.
"We don't understand the reason these systems are there," Gruber said. "As an academician, you'd love to investigate."
Although he likely won't ever fully examine every aspect of that discovery, he has been able to find a commercial application for some of what he learned. In 2009, he launched the biotech company Tensive Controls, a startup he relocated last month from North Carolina to Columbia.
He arrived in the midst of a 10-inch Missouri snowstorm.
After that faltering start, he is now ensconced in the University of Missouri Life Science Business Incubator at Monsanto Place and feels he has the resources he needs to take Tensive Controls to the next level.
Gruber made his original discovery while studying the human body's central melanocortin system. Melanocortin is the name given to a type of hormone produced by the pituitary gland in the brain; a hormone is a molecule that travels in the blood to tissues, where it binds to specific receptors, causing changes to occur.
Back then, Gruber's research was science for science's sake. "It had no immediate medical interest. It was interesting, but there are a lot of interesting things that have no application commercially," he said.
Gruber — who earned his doctorate in medical science from New York University in 1974 — has spent his career working as an academic researcher. He taught doctors for several years as a medical school professor and served as a branch chief at the National Institutes of Health between 1992 and 2001.
After his stint at the NIH, he left to continue his academic research at California Polytechnic University as an administrator. "I began to see that the melanocortin field had changed a lot since I left," he said.
Melanocortin first got its name because scientists were aware it controlled pigmentation. They were not yet aware these hormones regulate an array of physiologic processes.
"The pigmentation of melanocortins is one way to control body temperature in cold-blooded animals," Gruber explained. "Warm-blooded animals control their body temperature by metabolism."
But sometimes when animals are very, very sick, their metabolism rages out of control. When this happens to a human body, it manifests itself as cachexia, a wasting syndrome characterized by loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite. Even when a patient consumes more calories, lean body mass will be lost.
Cachexia is seen in patients with cancer, AIDS, chronic obstructive lung disease, congestive heart failure, tuberculosis and influenza. A healthy body searches for stores of energy first in its fat cells before it starts to rob muscles and organs for fuel. The body of a person suffering with cachexia doesn't care where the fuel comes from: The body cannibalizes itself at a cellular level. (This is called catabolism; it's the opposite of metabolism.)
Gruber compared cachexia to a house on fire.
"Your metabolism is running out of fuel, and it's like you are pulling out the wooden studs to keep the body's temperature up," he said. "It can get so extreme that a person can develop the symptoms of Kwashiorkor — a starvation disease — even if they are trying to get supplemental nutrition."
Gruber said some people die from cachexia before they succumb to cancer.
Donald Doll, a professor of clinical medicine at MU, sees a number of patients suffering cancer of the head and neck. Treatment can make it too painful to swallow, and often doctors turn to feeding tubes. But he said there's no magic bullet that controls cachexia, and the existing treatments "haven't been good."
"If you have a treatable cancer, controlling cachexia would allow the patient to tolerate radiation or chemotherapy long enough for the treatment to work," he said.
In the years since he left the field, Gruber watched many of his peers introduce drugs aimed at metabolism control.
"There have been many, many attempts to bring melanocortin drugs to market, but they failed in animal trials, and they failed in clinical trials," he said.
Why?
Although researchers were successful at controlling the body's metabolism, they were unable to prevent the deleterious cardiovascular side effects. And without that, the drugs were useless because even minimal degradations to the heart and lungs worsen over time.
Most researchers assumed the cardiovascular effects were part and parcel of the metabolic ones.
Gruber believes he is one of the first scientists to realize that assumption was wrong.
"Making melanocortin drugs has been tried before, but no one has tried — no one has our advantage — in understanding the cardiovascular effects could be separated from the metabolic ones. That was work that I had done years ago, but I hadn't figured out until just recently how to make a drug to do it," he said.
Once he realized he and his colleagues had the ability to develop a drug based on his previous work, he formed Tensive Controls. "In the same year, we got provisional patent protection for our technology," he said.
The company has three other equity-owners: Daniel Marks, a pediatric endocrinologist at Oregon Health Sciences University; Laszlo Prokai, a chemist at University of North Texas Health Sciences Center; and Michael Callahan, an expert in cardiovascular physiology and pharmacology at Wake Forest University School of Medicine.
Callahan remembers the day Gruber asked him to join him because it was Christmas 2008. "We had dinner and retired to the living room to talk about it," he said.
He was easily persuaded to join Gruber's team. He said scientists spend their days working on "pie in the sky" ideas.
"You hope some day your work will be important and interesting," he said. "This is closer than any number of things I've ever done to really impacting people's lives."
Gruber is convinced he has developed a drug that acts like a brake on a person's metabolism without affecting their cardiovascular system.
Now he has to prove his work to the federal government. Attempts to bring similar drugs to the market have failed at least 20 times.
"The FDA wants to have absolute evidence there's nothing affecting the cardiovascular system in any way," he said.
He said small animal tests done by Tensive Controls revealed the drug performed "exactly as we predicted."
"We stimulated appetite and began to restore lean body mass in a rat," he said.
Once he formed the company, he searched for a suitable business incubator. He settled upon Wake Forest University in North Carolina, but the move didn't work out, and he spent only six months there.
"We were told we would have full access to the animal facilities, and they took that promise back," he said.
Instead of fighting that turn of events, Gruber contacted the MU Life Science Business Incubator.
"I sent" incubator CEO and President "Jake Halliday an e-mail, and within two to three hours, I had a positive response," he said.
Halliday contacted Gerald Meininger, director of the Dalton Cardiovascular Research Center, who felt Gruber's research meshed well with the center's mission, particularly its expertise in cardiovascular pharmacology.
"It's terribly exciting whenever you can translate basic research findings into something that will be able to help patients," Meininger said.
Callahan said the move to Columbia is fortuitous because the Dalton Center scientists are world experts. "I don't know what forces were at work, but whatever it was, it feels like something was guiding us" to Columbia, he said.
When Gruber contacted the National Cancer Institute about the success he was seeing with his small-animal trials, the first question the institute's officials asked him was: "What are your plans for large animals?"
They were pleased to hear he was planning to conduct some experiments on companion animals, in coordination with the MU College of Veterinary Medicine, he said.
Gruber already has received $200,000 in Phase I NIH grants to do his work and $100,000 from the Patient Protection and Affordable Care Act of 2010. He is in the process of applying for Phase II grants, which he hopes will provide $2 million more.
He also will need private investment dollars to keep moving forward. "We're getting him ready to present to the Centennial Investors," Halliday said.
Gruber acknowledged that launching Tensive Controls — a startup with myriad challenges ahead — was a big gamble from his previous safe career as researcher and administrator. After all, those posts came with prestige and healthy salaries.
So, why do it?
He said it wasn't for the money. "I could be riding my bike around Europe right now, visiting the Hermitage," he said.
Instead, he is lured by the possibility of building a legacy for himself.
"At some point in your life, you realize you have more money than time," he said. "It's not about how you're going to spend your money, but how will you spend your time? How do you want to be remembered? I thought I could cure a few diseases."
