Genomica founder’s startup targets cure for heart disease

BOULDER – Body temperatures below freezing, but no bodily damage. A heart doubled in size in a few days without harm. Rapid fluctuations in hormones, massive enough to kill a human, but harmless to some creatures.

 Sounds like science fiction, but these natural adaptations, which occur in a few species, captured biologist Tom Marr’s attention.

Marr founded Hiberna, a Boulder-based biotechnology company, more than a year ago, in the hopes of discovering how these processes work and using that information to help humans.

“Hiberna is focused on taking advantage of novel evolutionary processes,´ said Marr, the company’s chief executive officer and chief scientific officer.

Funded by venture capital group Boulder Ventures, the research could lead to the creation of early detection tests for cardiovascular disease or for metabolic disorders, such as diabetes.

This isn’t Marr’s first shot at starting a biotech company. He founded Genomica in 1996 with capital from Boulder Ventures. Genomica sold to California-based Exelixis in 2002.

Kyle Lefkoff, a general partner at Boulder Ventures, said the research is onto something, but it’s too early to predict what will come out of Hiberna.

 “It’s going to be another year or so until we know if there is a marketable product there,” Lefkoff said, but he adds that Marr has hit the mark before.

“This is an interesting local startup, headed by a serial entrepreneur who’s been successful in the past.”

Hiberna’s research, currently in the early stages, is focused on two unlikely creatures: the Burmese python and the Arctic ground squirrel.

Examination of these nontraditional animals could yield big results, said Leslie Leinwand, Hiberna researcher and University of Colorado professor of molecular, cellular and developmental biology.

 “There are numerous animals that do extraordinary things, and I think it’s an untapped resource,” Leinwand said. The more common practice is to conduct research on mice and rats bred for use in laboratories but with less genetic diversity than naturally occurring animals.

Extraordinary things such as the Burmese python’s irregular eating patterns, which require the snake’s stalled metabolism to rapidly rev into high gear after consuming its infrequent meals.

“Pythons can consume meals that approach their body weight,” Leinwand said, leading to a raft of changes in the snake’s body.

For example, the python’s body floods with insulin by more than 40-fold, something that would kill a human. The snake’s heart doubles in size in just two days.

“And it’s new muscle, not just accumulating fluid,” Leinwand said, and then the heart returns to normal within a week. The rapid growth of the python’s heart interests Leinwand because disease-induced heart enlargement in humans is a good indicator of increased mortality.

“You can predict that these people with grossly enlarged hearts have a higher risk of death,” Leinwand said, and insights provided by python research could yield the key to drugs that can stop that enlargement, Leinwand said.

“The ability of the python’s heart to get bigger and then smaller could then lead to new therapies in humans,” Leinwand said.

Leinwand is currently screening pythons’ blood. 

“We want to find whatever it is in the python’s blood stream that the heart is responding to,” Leinwand said. It’s possible such a marker could lead to the development of a blood test to detect human heart enlargement without needing a tissue sample.

Leinwand and Hiberna recently received a $100,000 investment from the University of Colorado’s Technology Transfer Office to continue her research.

While a heart disease detecting blood test is still a long way off, Hiberna’s research could meet a huge demand.

“So if you look at the cardiovascular market, it’s billions in unmet needs that people have not been able to treat heart failure or detect it,” Marr said.

Marr and Hiberna linked with Leinwand more than a year ago, noting similarities between Leinwand’s python research and Marr’s research.

Marr spent three years at the University of Alaska, starting in 2002, researching the Arctic ground squirrel.

“A relatively small number of mammals are capable of doing this,” Marr said of true, or profound, hibernation. The ground squirrels he studied could hibernate for up to nine months, their body temperatures sometimes dropping below freezing and their hearts beating a mere four beats each minute. 

At the end of the hibernation season, the creatures rewarmed and began to function normally in a just a short time.

Discovering how squirrels survive the hibernation process without damage to their body systems could aid scientists in developing drugs to combat human diseases. 

Marr characterizes his ground squirrel research as “discovery-based” but with a lot of potential.

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