By Jennifer Burke
Treatment for tooth enamel erosion in the near future could be as easy as eating a lozenge or lollipop—not exactly candy—but medicine designed by a team of dental researchers at the UT Health Science Center.
The lozenge has the potential to be a game-changer for the dental profession. That’s due in large part to funding and commercialization guidance from the UT Research Foundation (UTRF), the non-profit organization that works with UT to bring innovations out of the laboratory setting and into the marketplace.
Thought to be the second oldest university research foundation in the United States, UTRF was originally founded in 1935 as the UT Research Corporation. Since its inception, UTRF has expanded from promoting innovations in agricultural to ones in energy, chemistry and materials, software and copyright, engineering, research tools and human health.
UTRF assists with invention disclosures across a broad spectrum of research disciplines – from sod to energy to human health. Examples include an assessment tool for adult educators, cell lines for immunotherapy, search engine methods for big data, a catalyst for energy production and disease resistant dogwood trees. During the past five years, UTRF has received 759 invention disclosures, executed 122 licenses to large established companies and fledgling startups and generated license revenue in excess of $12.2 million.
“Innovations can truly come from anywhere,” Stacey Patterson, Vice President for Research, Outreach and Economic Development at the University of Tennessee and President of the UT Research Foundation, says. “UTRF helps UT inventors advance innovations from their labs to the marketplace, benefiting society and creating economic impact, not just in Tennessee, but throughout the United States.”
Technology Transfer to the Private Sector
Assistance with the commercialization process is just one of many resources available to UT innovators and entrepreneurs through UTRF. With offices in Knoxville and Memphis, UTRF serves as a bridge between innovators in labs, clinics, greenhouses and classrooms throughout UT to industry, entrepreneurs and investors. This transfer of innovations to the private sector provides the public with the benefits of new products that are the result of academic-research, while creating new jobs and companies that boost the economy and producing income for innovators and the university.
“UTRF has been at the forefront of licensing technologies to companies that can take them to the next level.”
– Richard Magid
As a part of its mission, UTRF supports the growth of startup businesses in Tennessee. Prisma Renewable Composites, a spin-off of UTRF’s for-profit subsidiary TennEra, illustrates the growth opportunity for UT-affiliated startups in the region. Prisma creates advanced materials from lignin and other natural resources. In July of 2018, global pulp and paper company Domtar Corporation purchased a majority interest in Prisma to commercialize the use of lignin, the natural glue that bonds wood fibers, to make engineered plastic compounds. With a source for lignin secured, Prisma can begin to implement technologies it and UT researchers have developed during the past five and a half years.
“Prisma shows what’s possible when companies and university researchers join together to develop innovative solutions,” Maha Krishnamurthy, UTRF vice president, says. “UTRF supports Prisma’s efforts to build relationships with UT researchers who are developing technologies that one day will have a positive impact on society.”
The UTRF Business Incubator space on the UT Knoxville campus and the Innovation Lab Space on the UTHSC campus also play an integral role in UTRF’s support of Tennessee startup culture. Early stage tech firms spun out of university research benefit from these facilities, which provide affordable business space in an environment that supports entrepreneurship and assists with moving a company from the development process to self-sustainability.
“UTRF has been at the forefront of licensing technologies to companies that can take them to the next level,” Richard Magid, UTRF vice president, says. “When we facilitate agreements and provide business space, we’re driving economic development for the state and helping inventions enter the marketplace that positively impact our quality of life.”
The Path to Market
During more than two decades of practicing dentistry, Dr. Moideh Dehghan treated hundreds of patients for severe enamel erosion and she noticed one disturbing fact—they were all young. Teeth eroded by acid plagued the mouths of teenagers, children and college-age students alike.
The cause was clear. Dehghan could pinpoint why this typically senior condition was spreading to a younger population. A steady diet of acidic foods and beverages along with reflux and bulimia were the main culprits. The treatment, on the other hand, remained elusive.
“There was no protocol for treating acid erosion in this population and no specific home care products were recommended either.”
– Moideh Dehghan, DDS.
Without a proper treatment plan, otherwise healthy patients suffering from decay brought on by an increase in stomach acid had only one viable option—extensive, restorative dental treatment.
Dehghan thought there had to be a better way—a simpler, less expensive and less invasive fix. In 2011, she left private practice to join the UT College of Dentistry as an associate professor in the Department of General Dentistry to find the solution.
Collaborating with fellow researcher Dr. Daranee Versluis-Tantbirojn, Dehghan developed a safe-to-use mouthwash that neutralizes the acidic saliva and then helps to re-mineralize softened enamel. A patent was filed for the mouthwash in 2013 and granted in 2017. A later grant from the American Association of Women Dentists enabled a clinical pilot study to prove the mouthwash was more effective in reducing saliva acidity compared to other products already on the market.
While the mouthwash proved successful in toughening weak enamel, it had challenges in solubility (meaning the chemical properties of the mouthwash didn’t dissolve or break lose easily). Dehghan and Versluis-Tantbirojn collaborated with Hassan Almoazen to address the mouthwash’s solubility issues. They developed a double-layer solid lozenge or lollipop with the same components and same functionality of the mouthwash but in an easy-to-use, simple package.
The two layers of solid formulation that mimic a lozenge are made up of an outer layer amino acid, natural products and a flavor to neutralize the pH of the saliva while the inner core has similar solid formulation but has multiple crucial ions and a unique protein that enables the remineralization of the teeth enamel.
“The inner core has additional natural components combined with a flavor to exert a natural feeling to the patient,” Dehghan says. “The size of this lozenge can be scaled up or down based on age and weight of the patient and a plastic small stick can be incorporated to make it look like a lollipop for children.”
Dehghan, Versluis-Tantbirojn and Almoazen, anxious to continue researching the lozenge/lollipop, needed funding to proceed and applied to UTRF for assistance in the form of a maturation fund.
“We received the first $15,000 to develop the lozenge at the UT College of Pharmacy in Dr. Almoazen’s laboratory,” Dehghan says.
In 2017, UTRF applied for a US patent (pending) on the lollipop.
“Earlier this year (2018), we applied and received another UTRF grant for $30,000 to conduct clinical trials on acid reflux patients,” Dehghan says. “We’re currently in the midst of the clinical study and the preliminary results with the lollipop/lozenge are very promising. With the guidance and assistance of UTRF, we’re able to focus on our research while looking at different options for commercialization.”
Like Dehghan, Monica Jablonski, professor of ophthalmology, anatomy and neurobiology and pharmaceutical sciences in the UTHSC The Neuroscience Institute, was searching for a simple solution to a common medical problem.
Glaucoma affects more than 3 million people in the United States and is the leading cause of blindness in the world. According to the National Institutes of Health, an estimated more than six million people in the United States will have glaucoma by 2050.
“Elevated intraocular pressure (IOP) is one of the most significant risk factors contributing to visual field loss glaucoma,” Jablonski says. “IOP can be medically controlled through topically applied eye drops. This is usually the first-line therapeutic option, but current medications have a number of limitations.”
“Our technology will have a large impact on the treatment of ophthalmic diseases as the novel therapeutic can reach deep into the eye delivering anti-glaucoma agents to hard-to-reach target cells, and giving the gift of sight.”
– Monica Jablonski, Ph.D.
The medication does not address the underlying issues that lead to elevated IOP or the many genetic variations related to IOP modulation. It has a short half-life (time it takes for it to become 50 percent less active in the bloodstream) and doesn’t stay on the cornea for a long period of time, requiring patients to use eye drops multiple times per day leading to low patient compliance. And, the current eye drops result in high rates of corneal irritation, further impacting patient compliance.
However, UTHSC researchers developed a way to overcome those issues.
“We’ve discovered a new IOP lowering drug and developed a new microemulsion formulation that addresses each of these limitations,” Jablonski says. “Our microemulsion is designed to overcome the drawbacks of traditional aqueous eyedrops that are associated with rapid drainage, short corneal contact time and minimal corneal penetration; all of which lead to reduced efficacy, risk of corneal irritation and poor patient compliance.”
Jablonski discovered the new treatment while conducting research through a genetics study in collaboration with Rob Williams, Janey Wiggs and Lu Lu.
“We were searching for novel gene modulators associated with glaucoma and discovered a gene that modulates intraocular pressure in both mice and humans. Luckily for us, the gene encoded for a druggable protein. Even luckier, there was a Federal Drug Administration approved drug (pregabalin) that targeted the protein,” Jablonski says.
“When we put a drop of the drug on the eye, it lowered IOP in a dose dependent manner, but the effect didn’t last very long,” she continues. “Therefore, we designed a novel topical extended release delivery system to load with our drug. Using this new system, our drug lowers IOP by 40 percent and the effect lasts for a full day.”
In addition to Jablonski, the research team that discovered the novel topical extended release delivery system included Diana Johnson. The duo co-founded OculoTherapy in January 2014, a startup company that currently holds an option to take a worldwide commercial patent license from UTRF. Jablonski’s goal is to develop the formulation and bring the treatment to market. A patent for the formulation is pending and she anticipates the formulation can be coupled with other drugs to treat a range of eye-related diseases.
“We couldn’t do our research without UTRF,” Jablonksi says. “With their assistance in navigating the patent process and helping connect us with potential licenses, we’re able to potentially bring this invention to the marketplace.”
Through its UTRF Maturation Fund, UTRF has awarded Jablonski with grants in 2012 and 2018 to support glaucoma research efforts. In early 2018, Jablonski was elected as the first user of the UTHSC Innovation Lab Space, made possible by a partnership between the Memphis Bioworks Foundation and UTHSC.
“Our technology will have a large impact on the treatment of ophthalmic diseases as the novel therapeutic can reach deep into the eye delivering anti-glaucoma agents to hard-to-reach target cells, and giving the gift of sight,” she says. “The grant funding from UTRF made this life-changing research possible.”