September 2014

Building Momentum

We are pleased to share with you news of two new commercial licenses for Accelerator Program-supported technologies that have closed since our last newsletter. The first license is with Minnesota-based Segetis Inc. This privately held company is using levulinic acid from biomass to produce commercially useful chemicals. Segetis has licensed technology developed by Prof. Jim Dumesic that will help enable cost-effective production of levulinic acid. The commercial potential for this license is particularly encouraging because Segetis is already producing products derived from levulinic acid at commercial scale.

Our second license is for the Sundance cranberry developed by UW–Madison researcher Eric Zeldin. This variety has been licensed to multiple growers in the United States, but we were unable to address the market in Canada without proving that the variety can be grown effectively in that environment. The Accelerator Program supported a Canadian field trial, which has resulted in a license to Canneberges Ataboica Inc. to produce the variety in Canada. We believe that this variety will achieve strong acceptance in Canada as it has in the U.S. It is exciting to see this first license from our newest market focus area in Food Science. This brings our total to seven executed commercial licenses for projects supported by the WARF Accelerator Program, with four other technologies currently the subject of demonstrated commercial interest.

— Leigh Cagan, lcagan@warf.org

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Technology Monitor

Innovators look ahead to hybrid electronics, a new antioxidant, regrown bones and more


The WARF Accelerator Program speeds the advancement of technologies that hold exceptional promise for commercial success. With targeted funding and expert advice from seasoned business mentors known as Catalysts, the Accelerator Program helps inventions clear technical hurdles and advance to the marketplace. Following are the latest developments.

FOOD SCIENCE

• Combatting cheese browning: Parmesan has been one of the world’s most coveted cheeses since the Middle Ages, and today sports a billion dollar market. But the value of the cheese drops when it develops an unappealing “browning” effect that can’t be prevented by refrigeration.

Browning is caused by microbes that invade the cheese and produce a compound called methylglyoxal, finds Scott Rankin, a UW–Madison professor of food science. Rankin is investigating different tactics to inhibit the browning reaction, such as adding a reducing agent to cheese upon shredding.


Antioxidant prolongs shelf life: When unsaturated fatty acids and other lipids react with oxygen, food develops unappetizing odors, flavors and colors. The USDA estimates that more than 96 billion pounds of food may be thrown away in a single year due to the appearance of spoilage.

Meat, poultry and fish products are especially susceptible, and finding a way to prolong their shelf life could make a major commercial impact.

Mark Richards has a possible answer. The professor of animal sciences is investigating an enzyme, PLA2, found in commercial byproducts like pig digestive organs. Richards and his team have reached their goal of purifying PLA2 from porcine pancreas and obtaining a good yield. Their next step is to determine the best method to activate the enzyme and maximize its antioxidant power. Results using Lake Whitefish fillets appear promising.

Richards and his team are now assessing how the process could save costs.


Probiotic to fight intestinal bug: According to the National Institutes of Health, Clostridium difficile is a pathogen that causes diarrhea and more serious intestinal conditions such as colitis. Infections are known to spread in hospitals, and the elderly are particularly at risk.

James Steele, a UW–Madison food science professor, believes a solution could someday be found in the grocery store. His lab is investigating a "good bacterium," Lactobacillus casei, commonly found in yogurt and other foods. The Steele team is performing gastrointestinal analyses in animal models to identify the most promising strain for preventing and treating C. difficile infection. The strain could be ingested via dairy-derived foods.


COMPUTER SCIENCE AND INFORMATION TECHNOLOGY

Next generation electronics: Interest in graphene has grown rapidly due to its outstanding electrical properties. Graphene, a thin layer of carbon atoms, has the potential to outperform silicon-based semiconductors and herald a new class of high performance electronics.

But replacing silicon will require a commercially viable method for fabricating graphene. Materials science professors Michael Arnold and Padma Gopalan are investigating how to create large arrays of graphene nanostructures more than ten thousand times thinner than a human hair. A top-down approach has already shown promise. Their method uses electron beam lithography and chemical vapor deposition to carve graphene into nano-thick ribbons.

They’ve made an unexpected discovery along the way – it is possible to grow graphene nanoribbons from the bottom-up, directly on germanium wafers. Success could provide a direct route for creating hybrid graphene-silicon microelectronics.


Hybrid wireless system: Akbar Sayeed and Nader Behdad may be prototyping the future of telecommunications. The UW–Madison electrical and computer engineering professors have developed a new transmitter system called continuous aperture phased MIMO (CAP MIMO) that integrates both analog and digital processing. The result is a wireless communication system with superior power, wireless link capacity and bandwidth efficiency.

Based on feedback from Accelerator Catalysts and industry, the researchers say they are more confident and prepared to develop a scaled-up prototype.


MEDICAL DEVICES AND IN VITRO DIAGNOSTICS

Regenerating bones: The annual cost of treating musculoskeletal conditions tops $250 billion in the United States, with bone and joint diseases accounting for half of all chronic conditions in people over the age of 50. A new product being developed by biomedical engineering professor William Murphy takes aim at those statistics.

His team has created modular peptides that coat orthopedic implants and enhance bone growth at the implant site. The peptides could be utilized for spine fusion, dental care and certain types of fracture healing. Murphy’s latest publications have been widely viewed and presented internationally.


MRI detects iron overload: Iron is an essential nutrient for the human body but is toxic in excess. Iron overload is particularly hazardous to patients requiring regular blood transfusions. Accurate measurement of body iron levels is critical to prevent organ damage.

Radiology researchers Scott Reeder and Diego Hernando have developed a noninvasive method for detecting and quantifying iron overload in the liver using conventional MRI technology. Their method is fast, accurate and overcomes troublesome factors like background noise. Accelerator support has helped them acquire the early data they need to pursue a larger, multi-center study.


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Accelerator Chronicle

The delivery man


Researchers Jeff Lochhead and Robert Thorne are experimenting with a protein factor called MMP-9 to help deliver potentially lifesaving drugs to the brain.
Researchers Jeff Lochhead and Robert Thorne are experimenting with a protein factor called MMP-9 to help deliver potentially lifesaving drugs to the brain.
Can neuroscience breach the brain's defenses to combat anguishing diseases like dementia? The answer may take a backdoor.

But for Robert Thorne the devil's in the details and the journey is personal.


If science didn't caution against dreams, here’s a wild one: a father is succumbing to brain cancer. Yet there may be hope to save his life. His doctor recommends a drug – a large molecule like an antibody. He's prescribed a nasal spray and told to administer once a day.

Over time the medicine does more than patch up his ravishing symptoms. It defeats his disease.

His family calls it a cure, or perhaps a dream.

In a laboratory in Rennebohm Hall, Robert Thorne picks up the 700-page textbook he co-authored. The UW–Madison neuroscientist has sick brains on his mind.

"There are lots of potential drugs we can use to treat brain disorders like cancer, Alzheimer's, Parkinson's, you name it. Most major universities have big science programs that will go on identifying fantastic drug candidates."

The textbook hits the desk like a brick, rattling the papers and model globe.

"But at some point we have to get the drugs practically into the nervous system. The challenge, really for decades, has been the challenge of delivery."

He argues the fundamental problem is missing information. In the year 2014 the brain and its labyrinth of pathways continue to puzzle neuroscience.

The nasal passageway is one route to bypass the brain’s natural defense system to combat Parkinson’s disease and other afflictions.
The nasal passageway is one route to bypass the brain’s natural defense system to combat Parkinson’s disease and other afflictions.
"There have been a lot of people researching how to get big molecules and proteins into the brain but everything’s been a dismal failure. Why? Because we haven’t understood well enough how things work."

He feels this frustration as a researcher and as a son.

"My father died of brain cancer about 25 years ago. I know through that experience with him where the limitations are."

For more than two decades Thorne has been traveling the brain to understand its pathways, neurons, mechanisms and mysteries. His goal is to leverage this deep knowledge of anatomy and systems to discover the best inroads for medicine.

He explains that if the brain is a holy grail, it is guarded by a physiological fortress called the blood brain barrier.

"The blood brain barrier is the gold standard of barriers," says Thorne. "It's tight. It has all sorts of mechanisms to keep substances out."

The barrier shields the mammalian brain from the infinite hazards circulating through the body, permitting only a few molecules such as glucose to penetrate. But it's too much of a good thing. It also obstructs large, potentially lifesaving drugs like proteins and antibodies.

Picture a truck trying to get through a doorway, he says.

For this reason companies have focused on small, fat-soluble drugs taken orally that cross the intestine and slip into the brain through the bloodstream.

"The pharmaceutical industry has been bent on this model of drugs. So right there you should see the problem," says Thorne. "Any drug that isn't very small and fat soluble has not been utilized."

Bigger drug candidates – proteins, peptides, antibodies – have been left out in the cold.

Thorne and his team are pursuing an alternative strategy. Rather than trying to slip through the blood brain barrier, bypass it altogether.

There are several methods that attempt this, including neurosurgery.

"You may be surprised to find out that one of the state-of-the-art strategies we have for delivering drugs to the brain is sticking a catheter directly into the brain tissue," says Thorne.

Yet another method may be the most intriguing. Use the nose as a backdoor to the brain.

The neurons in our nasal passageways are surprisingly exposed to the outside world, Thorne explains. When you sniff a glass of wine, for example, scent-carrying particles called odorants drift into the nose and physically bind to receptors.

These easy-access neurons could serve as bridges to the brain for medicine. There’s a catch. The nasal epithelium is a barrier, and the larger drugs still have trouble penetrating.

Thorne and his team offer a solution. They realized that exposed neurons are vulnerable neurons, perpetually dying and sprouting like seedlings. How? A protein factor naturally found in the nose, called matrix metalloproteinase-9 (MMP-9), loosens the nasal epithelium like a fresh rain.

Spray the nasal passageway with an extra dose of MMP-9 and what happens? Will it help the big drugs pass through? Will the epithelium seal back up? Is it toxic?

Support from the Accelerator Program is helping Thorne take the next step and answer these critical questions using rodent models. His team, including research associate and co-inventor Jeff Lochhead, is tracking radioactive and fluorescently tagged antibodies through the animals' tissue to learn where they go, how they get there, and whether or not they actually end up in the right places in the brain.

"The Accelerator Program has helped me think about what could be done to enhance the prospects of finding an industry partner," says Thorne. "Having the chance to present the work to the biopharma Catalysts was a great experience."

For Thorne, his research has vintage appeal. The mere possibility of intranasal drug delivery was the topic of his thesis as a graduate student 20 years ago in Minnesota.

"The low-hanging fruit in science is always picked," he laughs. "The more headway we can make, the closer we get to what everybody in my field wants to do: finally have success."

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The Leading Edge

Catalyst redefines value, talks trust


Agriculture is fertile earth for entrepreneurs, although the future of meat production may surprise you. One thing's for sure, says Chris Salm, Wisconsin is the place to be.

At the age of 50, Chris Salm walked away from one of North America’s largest food companies to start his own business. Salm Partners, based in Denmark, Wis., is now leading changes in the meat industry. The company has more than 100 million pounds of production capacity and is winning over the crowd with collagen protein–encased sausages that are cooked in the package and ready to eat.

Q: What inspired you to take the leap from ConAgra and found Salm Partners in 2004?

A: I grew up on a large family farm. No, not a large farm. A large family on a farm. My parents had 12 kids. Part of the education was discipline and hard work. I always thought, why did we go through school and go off and work for other people? Why didn’t we start our own company?

I was approached by a supplier to the meat industry to see if I could help them, and I converted that conversation into a business model that has Salm Partners implementing technologies that suppliers spend their passions and lives developing. We implement those new technologies in full production systems, then turn around and supply the benefits to brand marketers.

Q: How did you get involved with the Accelerator Program?

A: Several years ago, the CALS dean and department chair of the meat science and muscle biology program were considering the future of the department. I became chair of an advisory committee and helped identify an expertise that UW–Madison could have that was unique and highly beneficial – finding value in animal agriculture that was not muscle related.

A lot people take the muscles of animals and convert them to food – wonderful, delicious, nutritious food. But there wasn’t anybody in the world, at least at the university level, creating a go-to place on the planet for finding value in everything else.

So we picked one species and asked the professors and staff, what's valuable in a pig that is not muscle? A group went through the literature reviews, did some thinking and came back with proposals. One proposal was pitched to Smithfield, the largest pork company in the U.S. The executives felt it was possible and potentially highly valuable. I was exposed to WARF folks from those conversations.

Q: What are some examples of non-food uses of meat?

A: In the pork industry heart valves are being harvested. There are components of the intestinal lining being harvested for tissue regeneration. There is a hernia patch that comes from the mesentery of sows that drives as much as $300 of value per animal, which is equivalent to the amount of money you get for meat out of the animal.

Q: Are there opportunities for entrepreneurs in this area?

A: Yes. The biological and medical implications are huge. I think at some point we are going to discover there is a single compound in the intestinal tract of animals that prevents them from getting cancer.

Q: This goes far beyond food science, involving expertise from other fields.

A: That's what makes Madison perfect. The med school, pharmacy school, bioengineering, animal science, vet school, microbiology, the business school, engineering, the hospitals…there isn't a university with that breadth of core, multidisciplinary expertise. This is why Wisconsin can be the go-to place on the planet for feeding the world better.

The future of food is this: how do we produce more for less cost? If we find valuable components in the rest of the animal then the meat doesn’t have to carry the economic burden.

Q: What do you mean by the "economic burden" of meat?

A: It costs a certain amount to raise an animal. For example, if it costs 10 dollars to raise an animal, right now nine dollars is covered by the people who eat the meat. The other dollar is covered by rendering applications or leather. If we find valuable components in the non-food stream then the meat becomes less expensive.

Q: What are the biggest challenges when scientists approach industry with their ideas?

A: Simply finding the right people to talk to in the segment you think you can influence. The most important thing is to have connections, contacts, relationships with people who you trust.

Q: Are you drawing on your experience starting your own business?

A: I draw on that every day. The ability to put ideas into a business model is extremely valuable. For the science community at UW–Madison, having that ability is so valuable. It's about taking your wisdom and knowledge and expertise and converting it into understandable economics.

Q: What's your favorite part of being a Catalyst?

A: It is fun meeting the huge brain power and extensive network of credible people. For me, just listening to some of the folks from other disciplines has been eye-opening and inspiring. The opportunity to listen to proposals and use my perspective on things to tease out potential avenues in the marketplace – it is fun.

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