Finding a more effective way to treat infantile hemangioma

Parents of a new baby are typically beaming with joy, at least when they are not excessively sleep-deprived. Such joy, however, can suddenly turn to worry if the baby develops an unusually bright red mark or a purplish, birthmark on their face, arms or anywhere on the body. The clinical diagnosis for these birthmarks is called infantile hemangioma, or IH for short.

Unlike conventional birthmarks, infantile hemangiomas typically change in appearance, first by getting bigger and then gradually resolving over several years. Infantile hemangiomas are the most common benign tumor found during the first year of life. They are diagnosed in about 170,000 babies born in the US annually, or between 1 and 3 percent of births.

About half the babies diagnosed with IH develop complications, but it’s not always easy to distinguish the infants who need treatment from those who don’t. Because most serious hemangiomas grow quickly, babies can develop scars even if the visible mark disappears. In other cases, breathing or vision may be impaired if a protruding mark appears on the nose or near the eye.

Parents of these babies are understandably anxious. Pediatricians often refer the families to a pediatric dermatologist, but even the most experienced experts acknowledge that existing beta blocker treatments are not optimal because they are absorbed systemically, especially at such a young age.

“We’ve been using two different beta blockers, propranolol and timolol, for about the past 15 years,” says Dr. Beth Drolet, a UW Health pediatric dermatologist whose clinical practice and research has focused on IH for three decades. “These drugs are usually effective, but they’re not ideal,” she adds, “More commonly prescribed for adults with heart conditions or high blood pressure, beta blockers can present several unwanted side effects.”

In addition, Drolet adds, parents need to feed the baby before each dose (every 3–4 hours), which means waking the baby during the night.

Goal is to develop a topical approach

The optimal solution, Drolet says, would be to safely deliver the beta blocker directly to the skin without it getting into the bloodstream.

As chair of the Department of Dermatology at the UW School of Medicine and Public Health, Drolet hasn’t been just waiting around for something better. She has, in fact, been at the forefront of developing a treatment methodology that could realize her dream and make life for these children and families much easier.

Working with a Madison-based biopharma company called Arkayli, co-founded by Drolet, she and her Arkayli colleagues see great promise for a new treatment, known as ARK001.

“The idea is fairly simple,” Drolet says. “Instead of giving the baby a liquid by mouth, parents can apply the formulation directly on the surface of the skin. The goal is to provide targeted treatment quickly and safely, before the hemangioma has a chance to cause bigger health or cosmetic problems.”

Fueled in part by a generous investment from UW Health Isthmus Project, ARK001 is still in early-stage development, although momentum for a safer alternative to existing treatments is clearly building.

Isthmus Project investment lends credibility

“This is a clever approach to an interesting problem,” says Elizabeth Hagerman, UW Health’s chief innovation officer and executive director of Isthmus Project. “Additionally, it’s a great fit for the Isthmus Project as we focus on supporting commercialization efforts of healthcare solutions developed by UW Health experts.”

Seth Reno – Arkayli President & CEO

Seth Reno, who joined Arkayli as president and CEO in 2021 after more than 30 years in the biopharma industry, was introduced to the project after meeting with Drolet and her two fellow Arkayli co-founders, Thom Rossi and Agis Kydonieus, both highly experienced drug development executives.

“This was clearly a strong team with a great idea,” Reno says. “Dr. Drolet sees hundreds of these patients each year and has been a key player in the evolution of infantile hemangioma treatment. This opportunity is exciting because we know that beta blockers are effective in treating IH. If we can more precisely treat babies with little to no systemic absorption of the beta blocker, and do it from the outside-in, rather than inside-out, the result would be a more effective treatment with minimal risk for systemic side-effects.”

Reno also credits Isthmus Project not only for its investment but its stamp of credibility.

“UW Health does not invest in projects on a whim,” Reno says. “They do extensive, thorough due diligence before making an investment. They’ve also provided added value by conducting their own market research which validated the need for such a product with pediatricians.”

Animal studies of ARK001 involving mini pigs, began in late 2022. Early toxicity studies are slated for 2023. Assuming these go smoothly, Arkayli’s next step would be seeking US Food and Drug Administration (FDA) for investigational new drug status, followed by clinical trials on infants with IH. “We’re not introducing a new molecular formulation,” says Drolet, “so our hope is that things will move forward at a quicker pace than if we were proposing a brand new drug. We’re hoping to reach the market by 2028.”

Published February 16, 2023

Innovative start-up Atrility sees growth for its AtriAmp device

As described in a 2020 article, Atrility’s signature device – the AtriAmp – provides continuous, real-time displays of the heart’s atrial signals. For patients, including babies, children and some adults, this means better outcomes because precious minutes are not wasted waiting for results from a time-consuming electrocardiogram (ECG).

Several recent developments bolster Atrility’s outlook, including (1) a financial investment in Atrility by Isthmus Project, UW Health’s innovation hub; (2) the hiring of Atrility’s president and CEO, Dave Kaysen; (3) UW Health becoming Atrility’s first customer, meaning that patients are already benefiting from use of the device at American Family Children’s Hospital in Madison; and (4) winning the grand prize of the 18th annual Wisconsin Governor’s Business Plan Contest.

Elizabeth Hagerman, Ph.D., Isthmus Project’s Executive Director and Chief Innovation Officer for UW Health, says the financial investment was made based on the great promise of the AtriAmp device.

“Dr. Von Bergen identified an unmet need in his own practice and, with his team, built a solution to improve the level of care available to patients of UW Health’s Pediatric Heart Program,” Hagerman says. “Our goal at Isthmus Project is to support UW-based health care innovation, so as we saw opportunity, Isthmus Project was eager to support Atrility in the next stage of growth and continued product development.”

Dave Kaysen

In March 2021, Atrility hired a new CEO, Dave Kaysen, whose 35 years of experience with small med-tech enterprises has already proven highly valuable. Kaysen credits Von Bergen’s original four-person team for producing an “elegant little product” with unlimited potential for growth.

“I was very impressed with what Nick and his team have done, which is why I was thrilled to sign on,” Kaysen says. “From design development to proto-typing to clearing the regulatory process to production, this small team rapidly advanced a value-added product in a relatively short window of time. Feedback from hospitals that are using the product on a trial basis has been very positive. We think the market for AtriAmp will only grow in the coming few years. Our job is to go out and make it happen.”

Kaysen is also excited to display the AtriAmp device in July at Heart Rhythm 2021, a convention in Boston sponsored by Heart Rhythm Society, a leading resource on cardiac pacing and electrophysiology. HRS

Not long after Kaysen became CEO, UW Health became Atrility’s first customer, making the AtriAmp device available in caring for babies and small children after having open-heart surgery. Physicians on the front lines confirm the value AtriAmp is adding to the care of babies and children in the pivotal hours and days following surgery.

“This is an extraordinary device,” says UW Health pediatric cardiologist Kathleen Maginot, MD. “We can immediately pinpoint the cause of an arrhythmia after a patient comes out of surgery. The AtriAmp allows us to evaluate detailed heart signals continuously rather than intermittently, then we can intervene right away when a patient might be in trouble. The consensus among our staff is, ‘How did we ever get by without it?’”

Maginot’s pediatric cardiology colleague, Dr. Margaret Greco, knows a good product when she sees one, having studied product design as an undergraduate.

“AtriAmp saves time while freeing up our busy colleagues who had to drop everything to do an ECG or atrial electrogram,” Greco says. “By greatly magnifying the heart’s electrical signals, we can catch problems much earlier and treat them accordingly.”

Published June 16, 2021

Taking the ‘pain in the neck’ out of performing surgery

Surgeons typically describe their work as challenging, fulfilling, rewarding and stimulating.

Many also will tell you that the job can be a real pain in the neck – literally.

To clearly see all they need to see while operating, surgeons have traditionally used a powerful headlight strapped to their forehead that is powered by a battery pack borne on the back.

Not surprisingly, 80 percent of surgeons say they experience significant pain during surgery. Half believe that wearing bulky headlights contributes to development of cervical spine disorders.

Five years ago, Josh Mezrich, MD, a UW Health transplant surgeon since 2007, was casually chatting with his neighbors, Madison business entrepreneurs Craig and Karen Christianson, when the couple asked Mezrich about life in the O.R.

Josh Mezrich, MD

“I told them my neck was killing me from wearing these headlights during surgery. Craig and Karen were intrigued and wanted to learn more,” Mezrich says.

It wasn’t long before the Christiansons encouraged Mezrich to partner with them to create a potential solution to this obvious problem.

Five years, thousands of hours, and more than 20 prototypes later, Josh’s simple idea has culminated in the MezLight surgical lighting device – an invention which is as stunning in its simplicity as it is in its utility.

Most surgeons hate headlights

“Every surgeon you talk with hates wearing the headlight,” says Mezrich. “We’re not pack horses. Not only does the headlight strain your neck, but it can pop out or get knocked out of place if you turn your head and bump into someone next to you.”

MezLight’s most liberating feature is that it takes the light off the surgeon’s head and mounts it to the side rail of the operating table. Like a modern day snake light for the O.R., MezLight’s flexible neck makes it easy to position and reposition endlessly. It then holds its position firmly, giving the surgeon a steady light source that won’t move when the surgeon moves. The device is also autoclavable, meaning it can be sterilized for repeated uses.

“You can easily move it to provide optimal light without getting in your way,” Mezrich says. “It’s also autoclavable, meaning it can be sterilized for several safe repeated uses.”

Mezrich and his team have received professional advice from UW Health’s Isthmus Project during the development of the MezLight.

“Isthmus Project provided us with guidance on several fronts, especially with regard to proper interaction with UW Health staff and avoiding any conflict of interest,” Mezrich says.

Other surgeons who have seen the MezLight prototype cannot wait to begin using it, and there is already a long list signed up to try it out.

The black MezLight lamp, mounted to the side of the operating table, is expected to greatly reduce neck pain for surgeons who are used to wearing a traditional surgical headlight.

Why didn’t someone invent it before?

“Surgeons simply can’t believe this hasn’t existed for years,” Mezrich says. “It’s so simple, yet nobody thought of doing it. And, with COVID forcing many surgeons to wear a face shield in the O.R., MezLight becomes even more beneficial because wearing a headlight with a face shield is nearly impossible.”

MezLight is looking to ship its first product before the end of the year, pending registration by the U.S. Food & Drug Administration.

While nothing is guaranteed, Mezrich hopes the product will become popular once surgeons start experiencing its benefits – bright light and no pain.

“I don’t want to change how surgeons operate,” Mezrich says. “I want to enhance how they operate.”

Bringing his idea to life would not have been possible without the Christiansons’ business expertise and the help of many other professionals and friends.

“It’s been exciting working with many great partners who have guided this effort. I was not fully aware of the complexity of making a product as seemingly simple as this a reality,” Mezrich said. “Participating in the process and watching it come to fruition is pretty cool.”

Published July 17, 2020

New UW-developed, arrhythmia-visualization device may save lives, prevent strokes and save hospitals money

As a UW Health pediatric cardiac electrophysiologist, Nick Von Bergen, MD, specializes in caring for children with abnormal heart rhythms, making him a highly valued resource who is often consulted after a child comes out of heart surgery – a time when arrhythmias are common and occasionally life threatening.

When a specialist like Von Bergen is called in, he focuses on achieving an accurate, rapid diagnosis with a constant eye on safety. To achieve the best outcome, Von Bergen depends on accurate interpretation of the signals coming from the heart’s electrical activity. Historically, this information is obtained from the bedside monitor or an electrocardiogram (EKG) in which electrodes are placed on the patient’s chest.

Currently the most easily accessible data source, EKG’s fall short of being a “gold standard” for identification of arrhythmias, especially when every minute counts.

Nick Von Bergen, MD

“In a typical case, I may be caring for a baby whose heart rate is spiking at 190 after coming out of surgery,” says Von Bergen, “I want to know if that spike is a response to the baby requiring more fluids, or if this is a potentially more serious abnormal heart rhythm we need to address. Unfortunately, bedside monitors are not precise enough and EKGs can take up to 20 minutes to set up. By contrast, a constant stream of real-time accurate data would help us diagnose heart rhythm immediately and treat the child much sooner,” Von Bergen says. “For pediatric and adult patients, having this information can save lives, prevent strokes and reduce hospital expense.”

Another EKG flaw, Von Bergen adds, is that the atrial, or upper chamber heart signals can be very hard to discern compared with the ventricular, or lower chamber heart signals.

“When we rely on bedside monitors,” he says, “discerning accurate atrial signals from an EKG can be like trying to see a small candle burning near a bonfire,” Von Bergen says. “The atrial signals are so small relative to the much larger ventricular signals.”

Alligator Clips, Wires and Duct Tape

Sensing an opportunity for improvement, Von Bergen was confident there had to be a better way to care for his patients. He began by cobbling together alligator clips, wires and duct tape. Calling it a “prototype” would be a stretch, but his instincts were in the right place.

It might be, thought Von Bergen, a good time to reach across the University of Wisconsin-Madison campus for some additional expertise. His first stop was UW’s Biomedical Engineering Department – a resource that he thought could further evolve his invention. Von Bergen also convinced UW School of Business senior lecturer Pete Lukszys of the potential for his idea. In 2017, Von Bergen and Lukszys, along with two Biomedical Engineering students – Matt Knoespel and Phil Terrien – formed a small business called Atrility Medical, to which Lukszys enthusiastically signed on as CEO.

Knoespel and Terrien, who impressed Von Bergen as having “the right stuff” to succeed as medical device designers, impressed Von Bergen with their work ethic, smarts, and desire to create things that help people.

“They also were excited enough about this ‘ground floor’ business opportunity to turn down more lucrative job offers, and we were lucky to have them as our first two full-time employees,” Von Bergen says.

The AtriAmp supports clear, continuous displays of atrial signals in real time.

Signature invention named “AtriAmp”

Von Bergen, Lukszys, Knoespel and Terrien – call them the Atrility Four – set out to turn Von Bergen’s original alligator-clip-and-duct-tape prototype into something potentially viable from a clinical, business and engineering perspective.

They designed a device named AtriAmp, short for atrial amplifier, which supports clear, continuous displays of atrial signals in real time.

“AtriAmp’s key feature,” Von Bergen says, “allows epicardial pacing wires, which get temporarily sutured to the heart during surgery, to deliver the highest quality rhythm signal to the bedside monitor, sparing us from reliance on lower quality signals or a long wait for EKG results.”

Early discussions took place with WARF (Wisconsin Alumni Research Foundation), which licenses intellectual property created by UW innovators.

Moreover, UW Health’s Isthmus Project, through its network of clinicians, investors and advisors, connected Atrility’s team with additional support and sources of valuable feedback.

Knoespel and Terrien dedicated themselves full-time to Atrility in 2018 after graduating from UW and spent about 18 months driving the product development. This meant getting up to speed on everything from electrocardiography to the many nuances of interacting with a federal regulatory agency.

“Phil and I appreciate the FDA’s (U.S. Food & Drug Administration) incredibly high bar for safety because of the high-risk situations in which our device will be used,” Knoespel says. “We had to reconsider a lot of things, and we understand why regulation is necessary for a device like this to achieve constant quality and safety.”

More Medical Devices Envisioned

The AtriAmp, just the first of what the Atrility team hopes to be a long line of innovative medical products, has received FDA approval and is expected to begin production by fall of 2020. Manufacturing will take place at a Wisconsin-based contracted manufacturer named Axcesor, located in Grafton, just north of Milwaukee.

“We are very proud that this product will be designed, produced and distributed by Wisconsin people,” Von Bergen says. “It really is a great example of the Wisconsin Idea in which the University seeks to leverage its expertise for the greater good of the state as a whole.”

Lukszys remembers what he told Von Bergen after initially hearing the physician’s presentation for his then-abstract idea for the AtriAmp  invention four years ago.

“I said ‘I think you’re on to something, Nick.’ ” Based on how eagerly physicians around the nation are awaiting their device, Lukszys and Von Bergen are on the right track.

Published July 17, 2020

Technology solution aims to extinguish provider burnout

It’s the hidden side of electronic health records: research shows that the average ER physician makes a mind-numbing 4,000 clicks per shift, spending nearly twice as much time on electronic record-keeping than they do directly working with patients, and clocking one to two hours of additional computer time after work to keep up with it all.

Joel Buchanan, MD, UW Health’s medical director of IT strategic projects, was convinced there had to be a better way — especially when working with patients with mile-long medical histories. Under the current system, if he wants to search for a patient’s cancer-related tests, he might have to sift through 140 lab results to find what he’s looking for. “Physicians can get overwhelmed, and that cognitive overload can contribute to clinician burnout,” he says.

Joel Buchanan, MD

Buchanan’s solution: a problem concept map that works with any electronic health record (EHR) system to filter only the most relevant patient information. This generates a Problem OrientedView. He turned to Thomas “Rock” Mackie, MD, administrator of Isthmus Project and UW Health’s chief innovation officer, for help turning his vision into a reality. UW Health’s new innovation accelerator not only provided business expertise, but also funds to kick-start the next stage of development. 

“When we show this to physicians they get very excited and want it tomorrow, but Rome wasn’t built in a day,” Buchanan notes. “There has to be an infrastructure of information to drive this new Problem Oriented View.” 

Buchanan has assembled a team of experts from six academic centers nationwide to create the knowledge bases that will allow an EHR to automatically sort information related to medications, labs, imaging, procedures, clinical notes and hospitalizations by condition. “The way this works is that a physician clicks on the problem — for example, epilepsy — and then the system uses one of these knowledge bases that we’ve created, and instead of showing all the medications a patient has ever taken, it shows just the four related to epilepsy,” he explains. 

For years, Buchanan has been passionate about encouraging physicians to adopt a problem-oriented medical record, a system that he believes leads to more efficient, quality care. He was further encouraged by his pilot study, supported by the National Institutes of Health, which found that physicians who used a problem-oriented system were able to find information more quickly, more accurately, with greater user satisfaction and less cognitive work.

Although Buchanan had been developing his idea for four years, his six months partnering with Isthmus Project in 2019 was like “the tinder to get the fire going,” he says. “Isthmus Project has helped me in several ways. One, it really helped guide me in a budgeting process, which is not something that comes naturally to a physician,” he says. “Isthmus Project has also provided some legal resources through arrangements with the UW Law School, and Dr. Mackie and others on his team have really acted as a cheerleader and confidence builder.” 

Buchanan initially approached Isthmus Project with the idea of starting a nonprofit organization. “But it really became clear that industry would be interested in this as well, so we helped him raise the money from the electronic health record industry and put together a term sheet for potential investors,” Mackie says. Ultimately, they decided that it made the most sense to keep it as a center within the university, with additional support from corporate and government sources. 

Seven EHR vendors have already signed on to provide financial support over the next three years — what Buchanan calls the “kindling” phase — as his team of medical experts works to achieve critical mass by creating approximately 200 maps. By 2022, he plans to establish a Center for Problem Concept Maps, which he hopes will be supported by the National Library of Medicine (the “fuel wood” stage) to ensure long-term viability and to make the technology available to institutions nationwide for a no-fee license. 

Without Isthmus Project, Buchanan expects it would have taken him as long as 12 years to reach the “kindling” phase, but Mackie helped him develop a plan to make it scalable more quickly. That means physicians — and ultimately their patients — will benefit sooner.

“Don’t be hesitant to reach out, even if you don’t have a formal business plan in place,” Buchanan says. “Dr. Mackie is very creative and energetic, and he’s certainly open to new ideas.”

Published November 18, 2019

Expanding the reach of life-saving cell therapies

After decades as a cancer researcher and hematologist, Jacques Galipeau, MD, was getting impatient to bring his discoveries from the laboratory to patients. “Patients are what motivate me and my team. I’ve published 179 papers, I’ve cured thousands of mice of cancer, and I’ve had enough of that,” says Galipeau, who is the director of the Program for Advanced Cell Therapy (PACT) at UW Health. “Our responsibility is not only to make discoveries, but when feasible, to bring them into practice to ease human suffering.”

Jacques Galipeau, MD

PACT provides targeted cell therapies for tough-to-treat conditions, and Galipeau spotted an opportunity to get the program’s discoveries to more patients more quickly. But he needed help navigating the unfamiliar territory from science to entrepreneurship.

Fortunately, he found the ideal guide in Thomas “Rock” Mackie, MD, administrator of Isthmus Project, UW Health’s new innovation accelerator. “Entrepreneurs have to be bold, and Rock is a bold thinker,” Galipeau says. “Rock understands the entrepreneurial business landscape in health sciences, and he has a track record of profitable experience. He’s been able to assemble the talent to come up with a road map so we can deploy these technologies in a sustainable way, which may eventually involve job creation and revenue generation.”

Mackie, UW Health’s chief innovation officer and an experienced entrepreneur himself, immediately recognized the potential in Galipeau’s work. He connected Galipeau to Isthmus Project’s partners, which include the WiSolve consulting group, UW-Madison’s Discovery to Product (D2P) office, the UW Institute for Clinical and Translational Research, UW-Madison’s Law and Entrepreneurship Clinic and UW-Extension’s Center for Technology Commercialization.

“We act as a bit of a tour guide of the entrepreneurial community, so we introduce researchers to various resources and supplement that with our knowledge of the medical industry,” Mackie says.

Isthmus Project and its partners helped Galipeau’s team with a market study, financial projections and regulatory work required to conduct clinical trials and eventually bring PACT’s cell therapies to market. 

PACT is now conducting two clinical trials to treat cytomegalovirus (CMV) — a common viral infection that can be fatal to those with very suppressed immune systems — in patients who have had bone marrow or kidney transplants. The kidney transplant trial is the first of its kind in the United States. “The idea is to take blood cells from an immune relative, purify them and give them back to you so your relative’s cells mop up the virus,” Galipeau explains.

The technology was first developed in Germany, where it has an 80 percent cure rate, but it’s new to the U.S. A better treatment for CMV is not only good for patients’ health — curing someone of the virus can save a substantial amount in healthcare costs.

“One of the interesting things about Dr. Galipeau’s work is that this is one of the few times when doing a clinical trial actually saves money,” Mackie notes.

Isthmus Project typically works with an entrepreneur for one to two years. “The longer you incubate something inside a healthcare system or university, the more successful it’s going to be when it comes out,” Mackie explains. 

After PACT can demonstrate that its cell therapies are safe, PACT will be ready to spin off a business that could eventually scale up and make the technology available to other hospitals nationwide. 

It’s just the first of many therapies that Galipeau envisions bringing to market. “PACT is the discovery engine,” he says. “Its progeny can then be launched off as stand-alone private entities that would be the model system for long-term development.”

While Galipeau doesn’t see himself ever filling the CEO role, he is excited about the potential of bridging the nonprofit and business worlds.

“There are a lot of cell-based therapies that could really move the needle in terms of patient outcomes but that may never be deployed because they don’t meet the profit margins that publicly held companies need to have,” he says. “As a nonprofit hospital, we’re judged on patient outcomes. If we can develop and market therapies that are at least break-even, it gives us a unique opportunity to develop technologies that otherwise might never be developed.”

Galipeau’s advice for others who might be mulling a business idea: Don’t wait. “You can’t discover something, put it on a shelf and wait for Prince Charming to develop it for you,” he says. “The biggest headwind for university scholars is they can let perfect get in the way of good, and they won’t reach out or think about reaching out until they achieve perfection. Father Time is your enemy. By the time you achieve perfection, your idea might not be patentable. You need to take ownership of developing your idea, and Isthmus Project can reduce the friction points to help you not only discover but develop new technologies for the benefits of patients.”

Published November 15, 2019