There's something about bears.
They can hunker down for winter, hibernate for up to six months, and wake up the next spring with bones that are as strong or stronger than when they settled in for a snooze.
It's a very different situation for humans. If they stay in bed for a time as short as two weeks bone loss sets in. For those with any kind of immobilizing disease, when it comes to bone density, the outlook can be dire.
Aursos, a 4-year-old Kalamazoo-based company, has licensed the technology developed by a Michigan Technological University professor Dr. Seth Donahue, who has been looking for the key for over a decade to what keeps bears' bones strong.
Pinpointing the answer could make all the difference to those who experience osteoporosis, spinal fractures, or seriously fractured long bones.
Dr. Donahue's findings to date support the idea that black bears have evolved biological mechanisms to fight the debilitating effects of disuse on bone. Bones in bears do not become more porous during hibernation, but appear to maintain their strength and actually grow thanks to parathyroid hormone, PTH.
In humans and bears, PTH has 84 amino acids. When
Dr. Donahue's team sequenced the gene for PTH they found there are nine amino acids that are different and it's believed that the bear has evolved its unique amino acid sequence to maintain strong bones during hibernation.
Dr. Donahue says as part of his research for Aursos, his lab has measured PTH in bear blood, cloned the gene for bear PTH, and used synthetic and recombinant bear PTH to reverse bone loss in rodent models of osteoporosis. Bones have gotten stronger in mice when PTH was injected over a period of weeks.
All the bear blood samples used in the studies were collected by Dr. Donahue's students at a lab at Virginia Tech, headed up by Mike Vaughan, now retired. Dr. Donahue says for safety sake they anesthetized the hibernating bears before taking blood samples since even a hibernating bear could wake up and things could get ugly if a researcher starts poking at it.
To get the drug to the next step, Aursos has partnered with another Kalamazoo life-science company, Proteos, Inc. to manufacture bear PTH1-84.
While the potential for such a drug is huge, Aursos' plan is to start out small and build. Before the company can offer a treatment for a huge market like osteoporosis it is moving into one so rare it's considered an orphan disease, Duchenne Muscular Dystrophy (DMD).
Each year, about 1 in 3,500 babies are born with Duchenne's. About 8,000 people in the United States live with the disease. Their immobility results in bones that are very brittle. Currently, there is no treatment for DMD.
Developing a treatment for youngsters born with DMD could mean fast-track FDA approval for a drug developed by Aursos. Chief Scientific Officer for the company, Dr. Ronald Shebuski, says the Muscular Dystrophy Association is highly interested in the potential for treatment that Aursos now is researching.
Shebuski, an experienced drug development scientist who directed Cardiovascular Therapeutics at Pharmacia and Upjohn, read about Donahue's research at Michigan Tech University in Houghton and went to meet the scientist. They started working together to develop bear PTH for a variety of health conditions.
"DMD, with orphan drug status, will be our initial entry into the marketplace," Shebuski says. Orphan drugs typically are those that cost more to develop than the company can recoup. Orphan drug status provides the company with important advantages, however, such as patent exclusivity and accelerated regulatory review.
Aursos' strategy is to use an approval in the smaller DMD market as a stepping stone to development of treatment for the larger markets, such as post-menopausal osteoporosis.
Osteoporosis is a health issue for about 44 million Americans -- 10 million with osteoporosis and 34 million with low bone mass who are at risk for osteoporosis. Those affected are expected to jump to 62 million by 2020 as the population ages. The osteoporosis market is forecast to be nearly $14 billion by 2014.
It's a market with a great deal of competition, however. Eli Lilly's Forteo, a human parathyroid hormone treatment, builds bone, and is the only drug on the market in the United States that does. The bisphosphonates, of which there a number of different formulations, including Boniva, do not build bone, but prevent bone loss in post menopausal women. They come with potential long-term toxicities, however. Another competitor, Amgen, also has a new drug in the market, Denosumab, which prevents bone loss.
Shebuski says it would take a trial of 4,000 women over four years, at a cost of about $100 million or more to get a drug to market that can treat post-menopausal osteoporosis, which is beyond the resources of the start-up company.
But once Aursos takes a drug to market that does not require such comprehensive testing, as would be the case for DMD, and shows it is safe and effective, the company hopes to partner with a big pharmaceutical company with the financial resources to undertake the kind of clinical trials necessary for the larger markets.
It's a model that has worked before. Aursos' new president and CEO is Gary Stroy, an entrepreneur with a great deal of experience getting new products to market. He's co-founded seven medical companies and most recently he successfully steered Afmedica's sale to Angiotech Pharmaceuticals.
Known as the "father of personal glucose monitoring," the founder of LifeScan, Stroy came up with the idea for the first pocket-size portable glucose testing device. It's now used by more than 10 million people with diabetes worldwide.
He is leading the company's current efforts to raise $10 million to carry the company through Phase II clinical testing of black bear PTH 1-84. During this phase, patients are treated to determine if a drug actually works and evaluate its short-term effects.
Right now, the company is attempting to raise the necessary funding from the venture capital community as well as seeking NIH grants and pharmaceutical partners to support the research.
Aursos also has the backing of the Kalamazoo-based
Apjohn Group, a life sciences business accelerator that offers resources to help companies get drugs and products to market.
Donald R. Parfet, Managing Director of the Apjohn Group, chairs the Board of Directors for Aursos.
Aursos has partnered with another Kalamazoo life science company, Proteos, Inc. to manufacture bear PTH1-84.
"This highly experienced drug development team has been successful before," Shebuski says, "and we believe we have another winner in Aursos."
Kathy Jennings is the editor of Southwest Michigan's Second Wave. She is a freelance writer and editor living in Kalamazoo.Photos by Erik Holladay.
Donald R. Parfet, chairman of the Board of Directors for Aursos. (Photo by Erik Holladay.)
A black bear could hold the key to stronger bones for humans. (Photo provided.)