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UConn Incubator Company’s Cardiovascular Connected Healthcare Provides A Solution for AFIB

Published by Med Device Online on 7/19/2017

Bob Marshall

Atrial fibrillation (also called AFib) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure, and other heart-related complications. At least 2.7 million Americans are living with AFib, according the American Heart Association (AHA). A worldwide study of AFib epidemiology from 1990 to 2010 estimated its prevalence at 33.5 million males and 12.6 million females in the year 2010.

During AFib, the upper chambers of the heart (the atria) do not beat effectively to move blood into the ventricles, which can result in clotting. If a resulting clot breaks off, enters the bloodstream and lodges in an artery leading to the brain, a stroke results. About 15–20 percent of people who have strokes have this heart arrhythmia, and this clot risk is why patients with AFib are often put on blood thinners.

The AHA provides these examples of how patients have described their experience:

“My heart flip-flops, skips beats, and feels like it’s banging against my chest wall, especially if I’m carrying stuff up my stairs or bending down.”

“I was nauseated, light-headed, and weak. I had a really fast heartbeat and felt like I was gasping for air.”

“I had no symptoms at all. I discovered my AF at a regular check-up.”

This third example is most troubling – due to a lack of symptoms and the intermittent nature of AFib, many people are unaware they have a serious condition that doubles the risk of heart-related death and is associated with a 5X increased risk for stroke. In addition, the prevalence of AFib increased by nearly five percent between 1990 and 2010, and the mortality rate doubled during the same time period, according to the above study.

Historical means of detecting AFib have included traditional electrocardiographs (ECGs) used during stress tests, Holter monitors, and event monitors. Holter monitors are portable ECGs worn to measure and record heart activity, continuously, over a period of 24-48 hours. The recordings then are reviewed by medical professionals to look for occurrences of AFib. Event monitors are used over a longer period of time (up to 30 days), and they are triggered by the patient when that patient experiences an irregularity, or “flutter,” and pushes a button to note the sensation. Recordings from just prior to the trigger are sent to medical professionals, who review the irregularity experienced by the patient and recommend further action, if necessary.

These means of monitoring are able to help identify whether a patient is experiencing AFib in some cases, but given the intermittent nature of the condition, such devices’ use for limited amounts of time can fail to capture proof of the cardiac rhythm problem. The electrodes attached to the skin can cause irritation — especially in the case of an event monitor, where the electrodes have to be removed and replaced every day or two over a period of several weeks. Additionally, it is a nuisance to remove Holter and event monitors for showering and bathing, and subsequently to reconnect them.

Cardiovascular Connected Healthcare Provides A Solution

All of these challenges led Dr. David A. McManus, an electrophysiologist and cardiologist at UMass Memorial Medical Center, to research with his colleagues and develop an alternative device. McManus is clinical director for Mobile Sense Technologies in Farmington, CT, as well as inventor of the company’s SensBand. The SensBand, claims to fill the gap between short duration adhesive monitors and long duration sub-cutaneous implants. It connects with the patient’s smartphone to provide continuous monitoring for AFib, and to enable data sharing with the patient’s doctor. Connected cardiovascular care provides a means to better engage patients in managing their own care, and is aimed at producing value-based outcomes. Detecting and monitoring AFib reduces stroke risk, improves the quality of life for patients, and reduces the overall cost of healthcare.

In 2013, McManus published in HeartRhythm the article A Novel Application for the Detection of an Irregular Pulse using an iPhone 4S in Patients with Atrial Fibrillation. In the piece, he describes a clinical study of 76 adult subjects with persistent AFib. Pulsatile time series recordings were obtained before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 different statistical methods. The sensitivity, specificity, and predictive accuracy of both algorithms were examined using the 12-lead electrocardiogram as the gold standard. An algorithm combining the 2 statistical methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during AFib from sinus rhythm.

The application was further evaluated in a study of 2000 people in India. McManus has stated that his goal is simple. He wants to keep people with AFib living longer and living well. “If the disease is diagnosed in time, it can go from life-threatening to an inconvenience – something you die with, not from,” he said.

UConn Biologist Takes New Tack Against Herpes Virus

Published by Hartford Business Journal on July 10, 2017

Matt Pilon

Herpes is more common than you might think.

The virus’ various forms affect most people, though they are often unaware. Herpes can remain dormant in healthy people but sometimes lead to serious or fatal conditions in infants or those with weak immune systems.

While there are no cures for the various forms of herpes, antiviral drugs do exist to curb its effects but there is a constant search for new remedies.

Among the researchers searching for answers is UConn Health biologist Sandra Weller, who chairs UConn’s molecular biology and biophysics department. Her lab is researching treatments for a form of herpes called Cytomegalovirus, or CMV, which can cause serious problems in newborns, including developmental disabilities and deafness, as well as infections in organ and marrow transplant patients. It’s estimated that more than half of adults have been infected with CMV by age 40, according to the Centers for Disease Control and Prevention.

An antiviral drug does exist to treat CMV patients — Ganciclovir — but some can build a resistance to it and the drug can also cause kidney problems.

Weller spent decades researching treatments for the more well-known genital herpes virus, but she shifted gears recently at the urging of a fledgling state-backed program called PITCH (Program in Innovative Therapeutics), launched by Yale and UConn to facilitate collaboration among researchers and venture capitalists and to speed promising drug compounds into the commercial pipeline.

“We consider [CMV] as having a larger unmet clinical need,” Weller said in a recent interview.

She and her team are targeting a particular protein that is believed to be essential for CMV to replicate itself. The goal is to find a natural or synthetic compound that can restrain the protein and prevent dormant CMV infections from reactivating.

Weller is working with Yale’s Center for Molecular Discovery because the school has a large library of drug molecules and enough capacity to work on multiple projects.

Last month, researchers at that lab began running a series of tests on Weller’s targeted protein using high-end equipment in a process called “high throughput screening.”

At the conclusion of their work, Yale researchers will tell Weller which compounds reacted with the targeted protein.

The screening services provided by Yale aren’t cheap. Weller would have had to seek funding to pay for them if it weren’t for PITCH, which received $10 million in late 2015 from the Connecticut Bioscience Fund, administered by Connecticut Innovations.

The technology originated at pharmaceutical companies and started becoming more common in higher education 20 years ago.

Market potential

While Yale could vastly narrow down the list of potential promising compounds, their findings won’t be quite ready for prime time.

From there the work will shift back to UConn, where Dennis Wright, a professor of medicinal chemistry and co-founder of PITCH, will assess the compounds and tweak their structures with the aim of making them more potent drug candidates.

“It’s about starting to put together a package of data that would make a compelling case to investors looking for an early stage opportunity,” Wright said.

Weller has already formed a company called Quercus. Her younger brother Brad Weller, an attorney who has worked for public companies, is CEO.

Should her research progress far enough, Quercus would license the intellectual property from UConn. If she gets an antiviral drug to market, Connecticut Innovations would receive royalty payments for its investment. There are several big pharmaceutical companies in phase 3 trials for CMV drugs, though they are targeting different proteins, Weller said.

Because CMV is a more complex strain of the herpes virus, Weller is hoping that whatever she develops might also be effective against other, simpler forms.

She likens members of the virus to cars. They all have the same core parts, but some, like CMV, have added features.

“It’s got a sunroof and a retractable antenna,” she said.

That makes CMV harder to work with, but offers a potentially more promising payoff.

Banned Invasive Plant Returning as Environmentally Safe Thanks to UConn Researcher

Published by Times Union on July 5, 2017

Brian Nearing

For the last two years, customers  have come into Faddegon’s Nursery asking Manager Randy Herrington for Japanese barberry, a popular landscaping shrub with pretty flowers.

And they have left disappointed, as Herrington has had to tell them the plant is an invasive species, banned from sale in the state since the spring of 2015.

Now, the barberry — one of 11 plants on the state’s banned invasives list — will be returning to nurseries, likely next year, thanks to research from the University of Connecticut that renders new variants of the plant sterile. Without seeds, the plant is unable to spread.

“We won’t have them now, but I expect by spring 2018, we will,” said Herrington. “It was a pretty big part of the landscaping market before the ban.”

Known scientifically as berberis thundbergii, barberries are spiny shrubs that are attractive, easy to grow and that deer do not like to eat, making them a popular choice with landscapers and homeowners.

Last month, the state Department of Environmental Conservation approved sales of four sterile versions of barberry, as well as sterile versions of two other regulated invasive plants, Chinese silvergrass and Winter Creeper.

That was welcome news to the New York State Nursery and Landscape Association, said Melissa Daniels, who is chairwoman of the group’s advocacy committee.

Her group had encouraged DEC, when the state adopted its invasive species ban, to leave open an exemption for so-called “sterile cultivars,” which means plants that do not produce seeds and consequently, eliminate the risk of seeds being spread by birds, other animals and water.

Such spread is a problem with barberry, where birds eat the bright red seeds each fall, and then move undigested seeds in droppings to sprout in new areas, such as fields and forests. There, the plants out-compete native species by crowding out sunlight and changing soil chemistry, which establishes new colonies that allow for continued spread.

By crowding out seedlings on the forest floor, barberry also can prevent forests from regrowing normally, according to DEC.  This concern also led to the banning of barberry sales in Massachusetts and New Hampshire.

While the new barberry plant would end this aspect of continued expansion, it will not keep the seeds from existing patches of fertile barberry from spreading into new areas.

Daniels said that barberry, which arrived in the U.S. as an ornamental plant in 1875 when seeds were shipped to Boston from St. Petersburg, Russia,  was a “very important commercial species” in New York.

An environmental group that sits on the state’s Invasive Species Advisory Committee also said the new plant should not pose a threat.

“Of course, we still encourage homeowners to plant native, non-invasive species,” said Troy Weldy, director of ecological  management for The Nature Conservancy.

Some alternatives include smokebush, eastern ninebark, weigela, and old fashioned weigela.

Weldy said the return of Japanese barberry will also require “honest labeling” by plant sellers, since the average homeowner cannot distinguish between a fertile and sterile barberry. “Our concern is that some people could again begin selling the non-sterile barberries. That could be a challenge,” he said.

The University of Connecticut recently obtained U.S. patents on four infertile, seedless barberry varieties created by researcher Mark Brand.

The university has an agreement with a Connecticut-based plant grower, Prides Corner Farms, to grow and sell the new varieties.

Prides Corner will be the supplier to Faddegons, said Herrington. “It will take them a while to propagate enough plants,” he said.

Another university researcher is seeking a patent for a sterile version of another popular landscaping plant, the burning bush. With the scientific name of euonymous alatus, this plant is also popular with homeowners for its vivid red autumn foliage.

As a state-regulated plant, it can be sold in New York, but must be labeled as an invasive species that is “harmful to the environment.”

Herrington said that once an infertile burning bush is approved, that plant will also be sold at his nursery.

Barberry has also been linked to increased tick habitat, because the plants provide ground cover to mice, which can carry ticks, and also maintain higher humidity levels that ticks need to avoid drying out, said Weldy.

More ticks increases the risk of transmission of Lyme disease and other tick-born illnesses.

Weldy said barberry needs to be present in dense stands to encourage higher tick populations. A few plants around a typical home likely would not be a risk, although the plants could provide cover for mice, he said.

UConn Alumna and TIP CEO Fights Cancer in Pets

Published by Fox 61 on June 27, 2017

Jenna Deangelis

FARMINGTON – Millions of cats and dogs get diagnosed with cancer each year, and a new treatment is helping to change their prognosis.

The revolutionary veterinary cancer treatment is called VetiVax and it uses the animals tumor cells to create a personalized treatment to help fight the disease.

The treatment helps trigger the immune system of the pet to help it recognize the tumor as foreign. It’s being used to help dogs, cats and horses combat cancer.

The company behind the treatment, Torigen Pharmaceuticals, was founded by UConn alumna Ashley Kalinauskas four years ago.

“This is my passion, this is my drive,” she said. “Were changing how pets are treated and this is a modality that can be considered when a pet is diagnosed with cancer.”

Kalinauskas said her graduate professor at Notre Dame, Mark Suckow began research on tissue vaccines in 2004. When his dog Sadie was diagnosed with cancer in 2010, she said he came up with this method to try and fight the disease.

“She had tumors growing almost all over her body and the veterinarians prognosis was take her home, enjoy her over Christmas and right after the holidays we’re gonna have to put her down,” Kalinauskas said. “He took a portion of Sadie’s tumor, created it into the personalized treatment, gave it back over a series of three weeks and he noticed the tumors started to recede.”

In two and a half years, Kalinauskas said 150 animals have been treated with VetiVax.

“We have unproven safety and unproven efficacy at the moment; however, what we do know is the animals have favorable outcome after being diagnosed,” she said.

One of those animals is a Yorkshire Terrier named Chloe whose owner Linda Levy told FOX61 since she’s been given the treatment, she’s had no signs of cancer.

“Unfortunately, we all know that the terrible thing of having a dog is that you know you’re going to see them go before you,” Levy said. “You just want them to have the best possible life and treatment if they get sick and I feel like I’ve been able to find that for her.”

Kalinauskas works at a dedicated laboratory space in Farmington through the UConn Technology Incubation Program. Her team members are also located in Minnesota and Arkansas.

The company works with veterinarians to treat animals around the country. The cost of VetiVax is $1200.

VetiVax can work for solid tumors including Melanoma, Squamous Cell Carcinoma, Fibrosarcoma, Soft Tissue Sarcoma, Hemangiosarcoma, Hepatocellular Carcinoma, Nasal Carcinoma, Osteosarcoma, Mast Cell Tumors, Basal Cell Carcinoma and Transitional Cell Carcinoma.

“It’s our belief that 10 years from now us as humans will start as our first line of defense with immunotherapies followed by the heavy hitters if it doesn’t work with chemotherapy and radiation,” she said.

UConn TIP Company Uses Microbiome For Innovative Skin Treatments

Published by Chemical & Engineering News on 5/8/2017

Marc S . Reisch

“Love your bacteria.” That’s the tagline for Yun Probiotherapy’s line of skin cosmetics directed at those who have acne or athlete’s foot or who just want to keep their skin looking healthy. Yun’s product line, now entering the personal care market, incorporates “friendly” bacteria to help correct skin microbe imbalances.

Scientists have known for some time that the skin, like the human gut, is teeming with bacteria, fungi, yeast, and viruses, all actors in what is known as the microbiome. Some are beneficial, others are not, and some considered “good” may become harmful under the right conditions.

There’s also long-standing evidence of a connection between a healthy gut and the consumption of Lactobacillus-containing supplements and foods such as yogurt. Research firm Global Market Insights estimates that the food market for the beneficial microorganisms known as probiotics exceeded $36 billion in 2015.

However, little was known about the diversity of the “bugs” among us or their impact on human health until the Human Microbiome Project, a five-year, $157 million endeavor launched in 2008 and overseen by the National Institutes of Health. The effort teased out tantalizing details on the astounding variety of microbial communities living in our guts and on our bodies.

Now, cosmetic formulators are taking tentative first steps toward applying some of the lessons learned from the project to develop their own microbiome franchises. They are designing health-enhancing skin care products that contain live bacteria, bacteria extracts, or ingredients meant to enhance skin microbe activity.

Skeptics say not enough evidence exists to verify the benefits of creams and butters meant to farm the bugs living on human skin. They especially question the benefit of placing live microorganisms on the body without thorough testing, and they wonder how formulations containing live actors can even exist when regulations generally forbid the sale of “contaminated” products.

Personal care product formulators like Yun aren’t put off by such questions about the skin microbiome. They see many opportunities emerging from research that suggests a strong connection between a balanced microbiome and healthy skin.

Others targeting consumers with skin-microbiome-enhancing formulas include start-up firms such as AOBiome, maker of skin care products containing the ammonia-oxidizing bacteria Nitrosomonas eutropha, and Gallinée, a supplier of products containing probiotics as well as so-called prebiotics that feed skin microorganisms.

And the small innovators are not alone. Some of the big personal care firms are staking out a claim to the microbiome. Johnson & Johnson, for instance, is helping the biotech firm S-Biomedic develop a bacterial treatment for both therapeutic and cosmetic applications. The firm is now a resident of J&J’s JLINX start-up incubator in Beerse, Belgium.

Procter & Gamble has taken an interest in the skin microbiome, applying for a patent on a prebiotic composition to “improve the health of the skin microbiome.” L’Oréal, meanwhile, has patented the bacteria-derived ingredient vitreoscilla ferment, intended to “balance” the microbiome of dry skin. The firm has incorporated it into cosmetics sold under its La Roche-Posay label.

Forward-looking personal care ingredient makers are also looking into what could be the next big thing in cosmetics. For instance, prominent ingredient suppliers such as BASF and Givaudan have introduced products to enhance the microbiome and, along with it, skin health. Smaller firms such as Azitra, Greenaltech, and Vantage Specialty Ingredients are also looking to provide microbiome-focused ingredients.

Microbiome skeptics

Not surprisingly, the concept of microbiome-enhancing cosmetics has its doubters. Wilfried Petersen, managing director of the German preservatives specialist Dr. Straetmans, wonders if the developing fascination with the skin microbiome will amount to more than a hill of beans. “The story of the microbiome sounds nice, but the proof of benefit is lacking,” he says.

European Union regulations, Petersen points out, don’t allow for the intentional addition of bacteria to cosmetics. In addition, he asks, if beneficial bacteria are added, how do you preserve the formula and how can you be sure it won’t become unstable and spoil?

Dermatologist Patricia K. Farris points out that skin microbiome imbalances, such as the overgrowth of Propionibacterium acnes, are prevalent in many skin diseases. Correcting those conditions, perhaps with lactic acid or other bacterial derivatives, can provide relief for people with those conditions.

“But can we make people look 20 years younger by putting probiotics on their face? I’m not sure we’re there yet,” says Farris, who is on the board of the American Academy of Dermatology. More study is needed to determine if pre- and probiotics are worthy of the hype they are getting, she says.

Studies carried out as part of the Human Microbiome Project suggest that a person isn’t so much an individual as a complex organism composed of both human and microbial cells. Trillions of microorganisms inhabit the body, outnumbering human cells by 10 to 1. In all, those microorganisms make up 1 to 3% of the body’s mass, or anywhere from 1 to 3 kg on the body of a 100-kg adult.

But the challenge is to translate that general knowledge into health and disease conditions and then to specific treatments. Mapping out and sequencing the genetic identity of microbes at various locations on the skin is a complex undertaking, notes Nava Dayan, a skin research consultant to pharmaceutical and personal care firms. Even with the work undertaken to date, “we don’t fully understand the baseline of what a healthy skin microbiome is because it varies from person to person and even differs depending on a person’s age and environment,” she says.

Without a full understanding of what the baseline is, developing a personal care product to influence the skin microbiome “is like shooting a moving target,” Dayan says. Even if scientists learn how the skin microbiome changes and shifts over time, they are still missing a lot of information about how microbes influence human cells.

Testing personal care formulations for their effects on the skin poses another problem, Dayan says. Cultured human cell models now used in labs “are inherently sterile.” It will be some time before scientists can develop a human cell model that also incorporates skin microbes.

Probiotic possibilities

Still, cosmetic firms such as Yun, the company that exhorts customers to love their bacteria, see value in harnessing what is now known about the microbiome. The firm has worked with scientists at the University of Antwerp to develop its product line, which incorporates live Lactobacillus. It promises to make its research public soon.

At a microbiome workshop last month at the In-Cosmetics personal care ingredients show in London, Yun cofounder Tom Verlinden said the company avoids contaminating other ingredients in its formula by housing the dormant Lactobacillus inside a protective microcapsule.

When the cream is rubbed on the skin, the capsule breaks open and the bacteria are activated, according to Verlinden, who is trained as a pharmacist. The firm uses a “natural” pH-activated preservative system that turns off when it hits the skin’s pH, he added.

Asked if he thinks the market is ready for skin care products that contain bacteria, Verlinden said he would not have thought so two years ago on the basis of surveys his firm conducted. “Now, given the fear of chemicals,” he said, consumers are ready for a more “natural” product.

Some consumers have already given Yun a vote of confidence. The firm raised more than $20,000 on Indiegogo, a crowdfunding website, earlier this year.

Regulators are ready for live probiotics too, Verlinden claimed. The regulators Yun has spoken with gave the firm the go-ahead after they saw data indicating its products “can’t hurt,” he says.

Also adding live bacteria to its formulas is Cambridge, Mass.-based AOBiome, maker of a product called Mother Dirt. Speaking at the London workshop, Elsa Jungman, a product manager for the firm, explained that company founder David Whitlock uncovered the ammonia-oxidizing bacteria after being challenged to explain why horses roll in the dirt.

Whitlock, a Massachusetts Institute of Technology-trained chemical engineer, took a look at the dirt and eventually isolated Nitrosomonas. While studying the bacteria, he found they consume the ammonia in sweat and produce nitric oxide and anti-infective compounds that have a role in regulating inflammation, Jungman explained. Whitlock concluded that horses roll in the dirt for its skin-soothing benefits.

Nitrosomonas were once common on human skin, AOBiome theorizes, but with the widespread use of surfactants to clean skin, they have all but disappeared. Reestablishing them on the body promotes skin health and reduces the occurrence of skin pathologies such as acne, Jungman claimed.

Mother Dirt drew attention the year before it was launched when a 2014 New York Times Magazine article detailed reporter Julia Scott’s experience testing a spray mist containing AOBiome’s active ingredient. After a month of using the mist instead of showering, Scott said, she didn’t smell and her skin changed for the better.

The mist and other preparations containing the bacteria contain no preservatives and must be refrigerated, Jungman said. “Our customers tend to be afraid of chemicals,” she said, and they tend to have very sensitive and problematic skin. To date, she noted, “we have had no adverse event reports involving our product.”

The biotech firm Azitra, a 2014 spin-off from Yale University, has developed a skin-soothing recombinant microbe based on Staphylococcus epidermidis, a normal part of the skin microbiome.

Azitra’s bacteria express filaggrin, a structural protein often missing or underexpressed in people who have skin problems such as eczema, explains Travis Whitfill, a Yale School of Medicine research scientist and Azitra’s chief science officer. The protein binds to keratin fibers in the skin’s epithelial cells, regulating skin lipids and helping the skin retain moisture, he says.

Whitfill says filaggrin production is designed to be short-lived. After a day or two, the bacteria “kick out” the designer DNA Azitra inserted as they reproduce on the skin. The bacteria are still there, but the altered DNA decays in the environment, he says.

Azitra is struggling with how to keep the bacteria viable until the consumer uses a product containing them. Whitfill says the firm is considering drying the bacteria so they go dormant and delivering them in a waterless emollient to the consumer. Moisture on the skin would revive them.

So far, Azitra has raised nearly $4 million from the venture capital firm Bios Partners, in which Whitfill is also a partner. Azitra aims to qualify a consumer product for sale by 2019, hopefully with another firm, Whitfill says. Longer term, it wants to develop its recombinant bacteria to treat skin conditions such as eczema and rare genetic skin diseases, he says.

Gallinée distributes a cream in France and the U.K. that contains what the company describes as “deactivated bacteria from the Lactobacillus family” along with prebiotic fibers and sugars to support the growth of good bacteria, and lactic acid to optimize skin pH. The combination of ingredients is intended to repair the skin barrier and support the microbiome.

The firm’s founder, Marie Drago, who like Verlinden is a pharmacist, also spoke at the London conference. Changing her diet to include prebiotic and probiotic ingredients alleviated the gluten intolerance she had for years, she claimed. That led her to reason that “if such a treatment worked inside, it could work outside too.”

“We’re cleaner than we used to be, and that’s why you see so much disease,” Drago said.

Active ingredient approaches

Some personal care ingredient suppliers are leery of diving into materials that contain bacteria, either alive or “deactivated.” But they are interested in developing active ingredients that work to benefit the skin microbiome.

“We considered developing live bacteria strains with skin benefits,” says Boris Vogelgesang, a technical manager at BASF, the world’s largest chemical company. But the firm was concerned about regulations on microbial “contamination” of personal care products and the complications inherent in preserving creams and lotions while keeping good bacteria viable.

“Maybe we can learn from food regulations,” which do allow active microorganisms in products such as yogurt and cheese, Vogelgesang suggests. “Preservative regulations need to evolve to distinguish good from harmful bacteria.” That may happen with time, but for now “it’s a brand new topic,” he says, and BASF is taking a conservative approach.

That approach includes establishing a research group that is exploring how microbes are involved in a healthy skin barrier and how active ingredients affect them. “We want to better understand the role of each microorganism in skin beauty and build new skin models to study effects of active ingredients,” says David Herault, BASF’s head of global R&D for bioactives.

Together with the International Center for Infectiology Research in Lyon, France, BASF has been developing skin models embedded with bacteria. The firm hopes the models will help it launch active ingredients to treat aging skin, skin with pigment disorders, and skin exposed to pollution as well as to work with different skin types.

BASF’s work in skin modeling also involves Poietis, a French firm with which it is developing a three-dimensional printed model of human skin as an alternative to animal testing of cosmetics, which is banned in Europe. Vogelgesang says 3-D printing can layer cells and precisely seed growth factors and cell types.

The technique might be adapted to reproduce the cells and bacteria found in wrinkles, Vogelgesang suggests. Such a model could lead to microbiome-inspired techniques to reduce skin wrinkling. “There is a lot to discover about the skin microbiome,” he says.

As BASF sees it, exploring the microbiome for personal care opens up a brave new world. “For years we’ve tried to eliminate problematic bacteria by using antibiotics. But killing the bad bacteria could also damage beneficial bacteria,” Vogelgesang says. “We need an approach that recognizes the community of flora on the skin and that preserves beneficial bacteria.”

For now the firm is using in vivo methods to look at the effect of active ingredients on skin microbes. In doing so it has come up with an ingredient, called Relipidium, that rebalances the skin microbiome. Vogelgesang says Relipidium works by encouraging growth of the beneficial bacterial S. epidermidis and discouraging growth of Staphylococcus aureus, which is associated with dermatitis and dry skin.

Launched late last year, Relipidium is made by feeding a yeast extract to Lactobacillus plantarum, a type of lactic acid bacteria. After filtering out any microbes, what are left behind are beneficial proteins, amino acids, and short-chain fatty acids.

BASF expects to develop products that complement Relipidium in the future, Vogelgesang says, adding that the firm’s likely next microbiome-inspired targets are ingredients that address oily and sensitive skin.

The fragrance ingredient specialist Givaudan is also developing actives to enhance the skin microbiome. Its 2015 acquisition of the active ingredients maker Induchem brought with it an R&D center in Toulouse, France, with expertise in genetic analysis and the microbiome, explains Fabrice Lefèvre, marketing and innovation director.

Givaudan initially developed Revivyl, one of its newest ingredients, to “revive” the skin by stimulating cellular differentiation and exfoliation of older skin cells. But then “we also asked how this ingredient would affect the microbiome,” Lefèvre says.

Isolated about 10 years ago, Revivyl is an extract from Orobanche rapum, a chlorophyll-free parasitic plant that grows in Europe. Besides its skin-reviving characteristic, Revivyl “protects skin by balancing the skin microbiota” and prevents microbial imbalances. According to the firm’s literature, Revivyl also inhibits the Finegoldia genus of opportunistic skin pathogens.

In a concept it calls [Yu] for “you are unique,” Givaudan is promoting the incorporation of Revivyl into fragrances. Such a use would combine a sensory experience with microbiome protection to make users “feel and look beautiful,” Lefèvre says.

Beyond ingredients that maintain the skin microbiome, Lefèvre says, Givaudan is developing ingredients that the microbiome turns on. One is Brightenyl, a skin-lightening agent that is activated by the skin’s resident bacteria.

Developed two years ago, Brightenyl contains an α-glucoside derivative of trihydroxybenzoic acid that Givaudan calls THBG. When applied to the skin, THBG is converted by certain microbes into trihydroxybenzoic acid, a molecule that evens out and lightens the skin.

Practical prebiotics

Other ingredient makers aren’t yet ready to go as far as introducing microbes to the skin or even developing ingredients that depend on microbiome activity. Many are betting that getting the skin microbiome into better balance with prebiotics is the first course of action.

“We stay strictly with prebiotics and address the skin holistically,” says Michael Anthonavage, technical director of Vantage Specialty Ingredients.

The firm’s PreBio Defense is a blend of polysaccharides that “acts as a fertilizer bed” for good skin bacteria, Anthonavage says. Prebiotics in the formula include inulin and β-glucan, which are packed into cellulose microcapsules to make it easy for formulators to blend into their skin care products, he says.

Greenaltech, a Barcelona-based biotech firm, is offering Algaktiv BioSKN, a prebiotic derived from microalgae. Joan Tarraga, who heads business development for the firm, describes BioSKN as a carbohydrate derived from microalgae cell membranes.

The skin is subject to a variety of assaults, including “sun radiation, urban pollution, weather, and chemicals in the environment,” Tarraga argues. As a result, the epidermis thins “and our microbiome is altered, leading to inflammation,” he says. Incorporated into a cosmetic formulation, BioSKN helps beneficial bacteria grow and reduces the proliferation of harmful bacteria that can cause inflammation, he claims.

Skin research consultant Dayan says she expects that scientists and cosmetic ingredient formulators will over time look more deeply into the “cross talk between the microbiome and human cells.” Understanding the complex community of microbes resident on the skin—and comprehending how those microbes can vary from individual to individual—can lead to the next steps in skin product development, she suggests.

It’s uncharted territory for the personal care business. For years people have been taught to fear bacteria and knew of only the infections and illnesses they could cause. Time will tell whether the public is now ready to accept skin care products full of bacteria and turn microbiome-inspired cosmetics into the next big thing.

Science to Startup: A Connecticut Company Plays the Startup Game in the Land of Innovation

Published in UConn Magazine in the Summer ’17 Issue

Colin Poitras

Biochemist Mark Driscoll is trying to crack open a stubborn microbe in his lab at UConn’s technology commercialization incubator in Farmington, Connecticut.

He needs to get past the microorganism’s tough outer shell to grab a sample of its DNA. Once he has the sample, Driscoll can capture the bacterium’s genetic ‘fingerprint,’ an important piece of evidence for doctors treating bacterial infections and scientists studying bacteria in the human microbiome. It’s a critical element in the new lab technology Driscoll and his business partner, Thomas Jarvie, are developing.

But at the moment, his microbe isn’t cooperating. Driscoll tries breaking into it chemically. He boils it. He pokes and pushes against the outer wall. Nothing happens. This drug-resistant pathogen is a particularly bad character that has evolved and strengthened its shell over generations. It isn’t giving up its secrets easily.

Stymied, Driscoll picks up the phone and calls Professor Peter Setlow at UConn Health. A noted expert in molecular biology and biophysics, Setlow has been cracking open microbes since 1968.

A few hours later, Driscoll jumps on a shuttle and takes a quarter-mile trip up the road to meet with Setlow in person. He explains his predicament. Setlow nods and says, “Here’s what I would do.”

And it works.

Breakthrough

That brief encounter, that collaboration between a talented young scientist and a prominent UConn researcher working in Connecticut’s bioscience corridor, not only results in an important breakthrough for Driscoll’s and Jarvie’s new business — called Shoreline Biome — but also leads to a proposal for more research, a new finding, and at least one patent application.

In a broader sense, it also exemplifies the collaborative relationships that UConn and state officials hope will flourish under the University’s Technology Incubation Program or TIP, which provides laboratory space, business mentoring, scientific support, and other services to entrepreneurs in Connecticut’s growing bioscience sector. At incubators in Storrs and Farmington, TIP currently supports 35 companies that specialize in things like health care software, small molecule therapies, vaccine development, diagnostics, bio-agriculture, and water purification.

The program has assisted more than 85 startup companies since it was established in 2003. Those companies have had a significant impact on Connecticut’s economy, raising more than $50 million in grant funding, $80 million in debt and pay equity, and more than $45 million in revenue.

“This is not a coincidence,” says Driscoll as he recounts his microbe- cracking story in a small office across the hall from his lab. “This is what government is supposed to do. It’s supposed to set up an environment where these kinds of things can happen.”

Bold Moves

Driscoll and Jarvie, a physical chemist and genomics expert, arrived at UConn’s Farmington incubator in June 2015 with a bold business concept but virtually no idea of how to get it off the ground. Both had worked in the labs at 454 Life Sciences in Branford, Connecticut, one of the state’s early bioscience success stories that ended up moving to the San Francisco area.

Driscoll and Jarvie decided to stay in Connecticut. They had talked about starting a business based on new technology that would more quickly and precisely identify different strains of bacteria in the human microbiome, the trillions of good and bad microorganisms living in our bodies that scientists believe play an important role in our health and well-being. The study of the microbiome is a rapidly growing area of biomedical research. There are currently more than 300 clinical trials of microbiome-based treatments in progress, according to the National Institutes of Health, and the global market for microbiome products is estimated to exceed $600 million a year by 2023.

“It’s the most frightening thing I have ever done,” says Driscoll with a chuckle. “As scientists, we know that nine out of 10 new companies fail. That sound you constantly hear in the back of your head is the ‘hiss’ of money being burned. The pressure is intense. You have to reach the next level before your money goes to zero because when the money’s gone, you’re done.”

Fortunately, Driscoll and Jarvie’s decision to launch a bioscience company came at a time when Connecticut and UConn were committing resources to strengthen the state’s bioscience research sector.

As part of Gov. Dannel P. Malloy’s Bioscience Connecticut initiative approved in 2011, Connecticut’s legislature allocated $864 million to efforts that would position the state as a leader in bioscience research and innovation. That initiative included the expansion of UConn’s technology incubator site in Farmington, the opening of The Jackson Laboratory for Genomic Medicine (JAX), and major upgrades at UConn Health to boost its research capacity.

Those resources were tailor made for a fledgling bioscience company like Shoreline Biome. Driscoll and Jarvie remember the early days when company ‘meetings’ took place at a local Starbucks, their official address and warehouse was Driscoll’s garage, and they didn’t even have a lab.

But they did have a vision of what Shoreline Biome could be. They knew that George Weinstock, one of the world’s foremost experts in microbial genomics and one of their customers at 454 Life Sciences, had just arrived at Jax. They reached out to him with an offer to collaborate. Weinstock not only agreed, he became their principal scientific advisor.

About the same time, Driscoll and Jarvie began exploring the possibility of renting space at TIP in Farmington because of its proximity to people like Weinstock and Setlow. “If you’re looking to start a bioscience company, in some parts of the state the cost for commercial space is going to be more than your will to live,” says Driscoll. “But here, the rent is graduated. So we were able stay here in the beginning for just a few hundred bucks a month.”

The pair also obtained $150,000 in pre-seed funding from Connecticut Innovations, the state’s quasi-public investment authority supporting innovative, growing companies; and a $500,000 equity investment from the Connecticut Bioscience Innovation Fund (CBIF).

Along with the pre-seed investment funds, CBIF’s staff helped guide Driscoll and Jarvie through the early stages of business development and introduced them to the investment community. AndCBIF member Patrick O’Neill took a seat on Shoreline Biome’s board. O’Neill’s business savvy has been crucial to the company’s early success, says Driscoll.

Tracking the Bad Guys

The lab kit Driscoll and Jarvie are currently testing is a low-cost, off-the-shelf tool that replaces hours of painstaking hands-on processing of patient samples for bacteria DNA testing. It’s about getting DNA out of the bacteria from a complicated environmental sample and doing that in a fast, cheap, and comprehensive way, explains Jarvie.

Researchers and medical professionals have previously relied on targeted testing and laboratory cultures to identify different bacteria strains. But many bacteria species are hard to grow in the lab, making identification and confirmation difficult. Even when scientists can confirm the presence of a bacteria such as salmonella in a patient sample, the findings are often limited, which can impact diagnosis and treatment.

“The DNA fingerprint region in a bacteria is about 1,500 bases long,” says Jarvie. “Most of the sequencing technologies out there are only getting a fraction of that, like 150 bases or 10 percent. It’s like relying on a small segment of a fingerprint as opposed to getting the entire fingerprint. You can’t really identify the organisms that well.”

Jarvie describes the difference this way. Say you are running tests for mammals on three different samples. Current sequencing technology would identify the samples as a primate, a canine, and a feline. With Shoreline Biome’s technology, the results are more definitive. They would say, ‘you have a howler monkey, a timber wolf, and a mountain lion.’

That level of specificity is important to researchers and medical professionals studying or tracking a bacteria strain or disease. Driscoll says the kit is not limited to identifying harmful bacteria like salmonella, listeria, or MRSA. It also can assist researchers investigating the microbiome’s role in maintaining the so-called ‘good’ bacteria that keeps us healthy as well as its role in other ailments such as diabetes, multiple sclerosis, and even mental health disorders like schizophrenia.

For example, the kit easily lets a researcher compare 50 bacteria samples from individuals with multiple sclerosis and 50 samples from individuals who don’t have the disease to see whether the presence or absence of a particular bacteria in the microbiome plays a role in impacting the body’s nervous system.

“If you don’t make it cost effective, if you don’t make it practical, people won’t do it,” says Driscoll. “It’s like going to the moon. Sure, we can go to the moon. But it takes a lot of time and money to build a rocket and get it ready. With our kit, all that stuff for the moon shot is already pre-made. We provide the whole system right off the shelf. You don’t need to know how to extract DNA fingerprints, or use a DNA sequencer, or analyze DNA. All you have to do is buy our kit and turn the crank.”

As part of their product testing, Shoreline Biome is working with researchers at UConn Health and JAX to learn more about a particularly toxic and potentially fatal intestinal bacterium, Clostridium difficile, otherwise known as C.diff.

“People who track this disease, especially in hospitals where it is a problem, want to know how it gets in there,” says Driscoll. “Does it come from visitors? Does it come from doctors? You have all these spores floating around. You can answer that by looking at the bacteria’s genetics. But if you can’t get to the bacteria’s DNA, you can’t identify it.

“Our tool cracks open the microbes so you can get at their DNA and fingerprint the bugs to see what you have,” says Driscoll. “It lets people see everything. And we’ve simplified the software so you don’t have to be a skilled microbiologist to do it. A person in the lab can sit down and with just a few clicks, all of this stuff comes up and tells you these are the bad guys, the infectious organisms that are present, and these are the good guys.”

Deer In the Headlights

While their focus is certainly on growing Shoreline Biome, Driscoll and Jarvie also have come to appreciate Connecticut’s broader effort in building a strong bioscience research core to help drive the state’s economy. Providing scientist entrepreneurs with an affordable base of operations, working labs, access to high-end lab equipment, and a cadre of science peers ready to help, takes some of the pressure off when launching a new company.

“This is all part of a plan the governor and the legislature have put together to have this stuff here,” Driscoll says. “You can sit around and hope that companies form or you can try to make your own luck. You set up a situation where you are likely to succeed by bringing in JAX, opening up a UConn TIP incubator across the street, and setting up funding. Is that going to start a company? Who knows? But then you have Tom and I, two scientists kicked loose from a company, and we notice there are all these things happening here. We could have left for California or gone to the Boston-Cambridge research corridor, but instead, we decided to stay in Connecticut.”

Mostafa Analoui, UConn’s executive director of venture development, including TIP, says the fact that two top scientists like Driscoll and Jarvie decided to stay in Connecticut speaks to the state’s highly skilled talent pool and growing innovation ecosystem.

“Instead of going to Boston or New York, they chose to stay in Connecticut, taking advantage of UConn’s TIP and other innovation programs provided by the state to grow their company, create jobs, and benefit society with their cutting-edge advances in microbiome research,” says Analoui.

UConn provides critical support to ventures at all stages of development, but it is especially important for startups, says Jeff Seemann, vice president for research at UConn and UConn Health.

When asked if they still have those moments of abject fear that they aren’t going to make it, Driscoll and Jarvie laugh.

“Every day is a deer-in-the-headlights moment,” says Driscoll. “Even when things are going well, it’s still a huge risk.”

“It never goes away,” agrees Jarvie. But during a recent visit to the Shoreline Biome lab, both men are in good spirits.

The company met the 12-month goals set in their CBIF funding agreement in just six months. For that effort, Driscoll and Jarvie received another $250,000 check, the second of their two CBIF payments.

In the world of business startups, however, there is little time for extended celebration. The two scientists mark the milestone with smiles and a fist bump, then turn around and get back to work.

UConn Student Engineers Monitoring System for Bridges

Published on UConn Today / May 26, 2017

Claire Hall

Kevin McMullen, a structural engineering Ph.D. student at UConn, has designed a bridge-safety monitoring device.

Kevin McMullen, a structural engineering Ph.D. student at UConn, has designed a bridge-safety monitoring device.

In the middle of a June night in 1983, a 100-foot span of the Mianus River Bridge in Greenwich, Conn., collapsed, plunging two cars and two tractor-trailers into the river 70 feet below.

Three people died, three were seriously injured, and diverted I-95 traffic snarled local streets for six months. Inspections revealed that an undetected fatigue crack caused the catastrophic bridge failure.

Kevin McMullen, a structural engineering Ph.D. student at UConn, is too young to remember that tragedy. But he has designed a bridge-safety monitoring device that might have prevented it. He’s hoping his company, NexGen Infrastructure, can revolutionize transportation safety.

Using force-sensing pads that continuously monitor bridges, the system can warn engineers about a bridge that is overstressed. The pads can be installed on a new bridge or one that is being repaired. The system doesn’t replace human inspection, but can help establish priorities in a nation where one in 10 bridges is structurally deficient.

“Our hope is that if something is going drastically wrong with a bridge, engineers would be alerted that the bridge needs to be inspected right away,’’ he said. “We are anticipating that the federal government and state departments of transportation will feel it is a worthwhile investment.’’

McMullen recently received a $40,000 grant from the UConn School of Engineering in partnership with Connecticut Innovations. This award is given to engineering students with promising technologies, to help them enter the marketplace. Ironically, the award is called the Third Bridge Grant.

“Not much has changed in infrastructure over the last few decades,’’ McMullen said. “More recently, new technologies are being developed for infrastructure and civil engineering. This push towards innovation makes me know I’m in the right field.’’

McMullen, who earned a bachelor’s degree in civil engineering from UConn in 2015, smiles when asked how he developed his passion.

“As a kid, I built with Legos and loved creating things,’’ he said. “When I decided what to study at UConn, civil engineering was the choice for me. And for some reason, I’ve just always loved bridges.’’

He is working on a Ph.D. thesis about a new, streamlined bridge-repair process that would be more cost-effective and minimize traffic disruptions.

“Many people surrounding me at UConn, including Professor Hadi Bozorgmanesh, who teaches an entrepreneurship program for graduate students, and my adviser, Professor Arash Zaghi, have really pushed innovation and got me thinking out of the box,’’ said McMullen.

“UConn has been very instrumental in getting my company off the ground. The Third Bridge grant I was awarded is helping me to start my company and bridge ‘the valley of death,’ so when I leave UConn, I can hit the ground running.’’

UConn Research Innovation Newsletter – June 2017

Check out the latest UConn Research Innovation newsletter to learn about exciting technologies and startups with a UConn connection.

UConn TIP Farmington Startup Sets Sights on Curing Retinal-Disease Blindness

Published on UConn Today / May 24, 2017

Claire Hall

Nicole Wagner, president and CEO of LambdaVision, which was founded through support from UConn’s Technology Commercialization Services in 2009.

Nicole Wagner, president and CEO of LambdaVision, which was founded through support from UConn’s Technology Commercialization Services in 2009.

Tucked inside a small laboratory at UConn’s Technology Incubation Program (TIP) in Farmington, Conn., Nicole Wagner is trying to cure vision impairment and blindness for more than 30 million people worldwide.

Using a protein, grown in the laboratory and implanted behind the retina, this promising new procedure offers hope for patients with age-related macular degeneration (AMD) and other retinal diseases.

“These are terrible diseases that truly impact the quality of life for many people,’’ said Wagner, the president and CEO of LambdaVision. “To offer patients the possibility of restoring their vision provides them the chance to see a new grandchild, resume a golf game, drive again or read a favorite book. For many people, restored vision would allow them to return to an independent life.’’

LambdaVision uses a light-activated protein, bacteriorhodopsin, to stimulate the retina of patients suffering from impaired or lost vision due to retinal degenerative diseases. The protein, isolated from high-salt environments, including the Dead Sea, is grown and purified in the laboratory. The protein works by absorbing light and converting it into a signal that is picked up by specialized cells in the retina, relayed to the optic nerve and ultimately interpreted by the brain.

More than 31 million people worldwide suffer from irreversible vision loss caused by macular degeneration and retinitis pigmentosa. The incidence of blindness caused by retinal degenerative diseases is increasing at a rapid rate due to an increase in the global geriatric population, Wagner said.

LambdaVision’s implant can restore high-quality vision to those patients who are no longer candidates for traditional treatments and have end-stage retinal degeneration, Wagner said. Current treatments only succeed in slowing the progression of disease.

LambdaVision was founded through support from UConn’s Technology Commercialization Services in 2009. Dr. Robert R. Birge, distinguished professor of chemistry at UConn, led a research group that included Wagner.

The protein is in pre-clinical trials across the country to determine the stability and efficacy of the implant.

“LambdaVision has been incredibly fortunate to have the continued support of UConn and the State of Connecticut, and we owe much of our success to the incredible mentors that have helped us to propel the research and development and commercialization of the technology,’’ she said. “In the early stages of development, they were the believers.’’

LambdaVision has won many awards, including most recently: a 2016 UConn SPARK Technology Commercialization Fund Award and the prestigious 2016 MassChallenge CASIS-Boeing Prize for Technology, which allows the company to carry out experiments aboard the International Space Station. Since gravity can interfere with the uniformity of the retinal implant films, the hope is that work done in microgravity will be faster and yield improvements in the homogeneity and stability of the product.

The company also won the $15,000 Wolff New Venture Prize, sponsored by UConn’s Connecticut Center for Entrepreneurship and Innovation (CCEI) and a National Science Foundation Small Business Innovation Research Grant.

“To be on the brink of a new and exciting medical breakthrough is thrilling,’’ Wagner said. “I’m very eager to see this technology available in the medical community where it can make a difference in people’s lives.’’

UConn Technology Incubation Program Company, Torigen, Inc., among Other High-impact Startups Participating in MassChallenge 2017 Cohort

Published on MassChallenge / May 23, 2017

MassChallenge, the most startup-friendly accelerator on the planet, today announced the 128 early-stage startups that have been accepted into the 2017 MassChallenge Boston accelerator program. Selected by a community of more than 850 expert judges, this year’s competitive cohort represents the top 8% of applications from around the world, including 12 countries and 16 U.S. states.

Through a global network of zero-equity accelerators, MassChallenge helps the world’s highest-impact, highest-potential startups successfully launch, grow, and create impact across industries. This proven model has accelerated 1,211 alumni that have gone on to raise more than $2 billion in funding, generate approximately $900 million in revenue, and create over than 65,000 direct and indirect jobs.

“The quality of this year’s applicant pool is a real testament to the community’s efforts to inspire and support individuals who are working to solve some of the world’s biggest problems,” said Kiki Mills Johnston, Managing Director, MassChallenge Boston. “I’m excited to welcome the 2017 cohort to Boston this summer. This is just the beginning!”

Since March, top investors, serial entrepreneurs, corporate executives, academics, and more have evaluated over 1,500 applications based on each startup’s ability to demonstrate impact and potential, which ranges from scientific breakthroughs to industry disruptions. Many of these judges remain actively involved throughout the four-month MassChallenge Boston program as mentors, speakers, and even potential partners.

Of the 128 startups selected:

  • 30% are healthcare and life sciences
  • 29% are high tech
  • 20% are general, retail and consumer goods
  • 16% are social impact
  • 6% are cleantech and energy

As part of the 2017 cohort, startups will have unrivaled access to top corporate partners, expert mentorship, tailored curriculum, and more than 26,000 square-feet of co-working space in Boston’s dynamic Innovation and Design Building – all at zero cost and for zero equity. Entrepreneurs developing physical products also have an opportunity to take advantage of MADE @MassChallenge, the organization’s 5,000 square-foot research and development lab, which provides the equipment and support needed to design, develop, and scale hardware solutions.

The accelerator program will culminate on November 2, 2017 at the MassChallenge Boston Awards, where the most-promising startups compete for shares of more than $1.5 million in equity-free awards.

“Over the past seven years, MassChallenge has graduated more than 1,200 entrepreneurs from our intensive accelerator, enabling them to create enormous impact around the world,” said John Harthorne, Founder and CEO of MassChallenge. “We are proud to welcome such a high-potential class of startups to MassChallenge, and are excited to help them define their future and maximize their impact.”

Now in its eighth year, MassChallenge has continued to drive innovation around the world through its global network of accelerators in Boston, Israel, Mexico, Switzerland, and the U.K. In addition to existing programs, the organization experienced significant growth in 2016 with the launch of several new initiatives. Locally, MassChallenge Boston launched the Newton Innovation Center, a 5,000 square-foot co-working space in collaboration with CIC and the City of Newton, and PULSE @MassChallenge, a zero-equity innovation lab that connects digital health entrepreneurs to the region’s leading institutions, corporates, payors, and healthcare experts. Top startups from the first-ever PULSE @MassChallenge cohort will compete for shares of more than $200,000 in equity-free awards at PULSE Finale on June 13, 2017.