The otolaryngology treatments of tomorrow are the research of today, but somebody has to pay for it.
Explore This IssueSeptember 2011
That’s where the grant programs of the Triological Society come in. The society, which has awarded more than $2.5 million in grants since 1994, promotes research into the causes and treatments of ear, nose and throat diseases via two funding streams: the Career Development Award, which provides up to $40,000 for research career development support over a one or two-year period, and the Clinical Scientist Development Award, which is co-sponsored by the society and the American College of Surgeons (ACS) and provides $80,000 per year for up to five years to surgeons already awarded a National Institutes of Health (NIH) Mentored Clinical Scientist Development Award (K08/K23).
Both grants cater to young otolaryngology-head and neck surgeons who can use them as springboards. ENT Today talked to the nine physicians awarded last year’s grants to learn how they used their funding, and, perhaps more importantly, how it has helped their careers.
CAREER DEVELOPMENT AWARDS
Born with a penchant for engineering, Dr. Adunka has focused his research on developing technology that will allow intracochlear electrode implantation with little or no trauma, “so we can combine the natural hearing with the cochlear implant.” The end goal, he said, is to incorporate an “upgrade” into current cochlear implant technology that would allow otolaryngologists to improve electrode placement.
Dr. Adunka and his team began this research in 2006 in humans but reverted to the animal model soon after due to a lack of qualified participants. The project will collect animal data for a few years, “but in parallel we want to move back to a clinical setting to test the true value of this technology,” he said, adding that his team is working on developing a solution with all three manufacturers of cochlear implants (Cochlear Limited in Australia, MED-EL in Austria and Advanced Bionics in the U.S.). Dr. Adunka’s goal is to “modify” existing technology to better record, measure and adjust to residual acoustic hearing.
The Career Development Award revived a near-dead project, Dr. Adunka said candidly. He and a collaborator, who had previously been funded through an NIH grant, lost that backing partly because of the economic downturn of the past few years. “Getting the grant has really helped us to keep this research going,” he said.
But he’s not stopping there. Dr. Adunka said the team plans to continue collecting preliminary data and expects to submit a new proposal to NIH in June. “It worked out perfectly,” he said. “We’re right on track …we had some difficulties early on, but everything is going the right direction.”
Allergens have long been studied as a contributing factor to laryngitis, particularly in those patients who present chronic laryngitis without a clear etiology. Dr. Belafsky is taking that idea one step further, examining the role of the environment in laryngitis.
“The idea that allergens can affect the lungs and larynx is not novel,” he said, “… but the concept that allergens and pollution work synergistically to affect the larynx and esophagus is.” He added that his research “may provide new insight into the etiology of the current pandemic of chronic laryngitis and esophagitis.”
Dr. Belafsky is using 24 guinea pigs divided into four study groups to examine the impact of the environment on the larynx and esophagus. One group is being exposed to dust mite allergens, another to combustion particles simulating pollution and a third to both agents combined. The fourth set is a control group. The animal exposures have been completed, and preliminary data suggests that the combination of sensitized allergens and combustion particles causes pan-eosinophilia in the larynx.
“This will be the first description in the literature of eosinophilic laryngitis,” Dr. Belafsky said. “The future? In an animal model, we’ve described eosinophilic laryngitis. We need to see if this is a true disease entity in humans.”
To make that next step happen likely means more funding. And for “grateful” physicians like Dr. Belafsky, the Career Development Award is often seen as a stepping stone to that money, particularly in the form of NIH grants.
“The NIH is not going to fund this preliminary work,” he said. “It is difficult to secure support for such a high-risk project in this environment.”
Dr. Chen is using a new technology to measure oxygen levels in tumors and tissue as a tool to individualize cancer treatments and improve wound healing in patients. Her grant is paying for an animal model looking at radiation-induced tissue hypoxia.
The funding “is tremendously important,” she said. “Otherwise this research wouldn’t be able to go through.”
Dr. Chen said being able to identify and track oxygen levels in both tumors and tissue could have a “huge impact” on improving therapeutic ratio for cancer patients. “If you could just monitor the level of oxygen and know that if it is below a certain level, you should hold off on radiation treatment … because it is really causing more damage than good,” she said.
This “oxygen profiling” also has surgical applications because wounds need oxygen to heal, and surgery on hypoxic tissue could lead to complications. “Being able to know that would be incredibly helpful,” she said. “There are really few other methods to track the oxygen level, which is why the value of this research really could have an impact on treatment and outcomes of anybody who has radiation and/or surgery.”
Dr. Chen and colleagues are using a noninvasive technique to measure oxygen in the tissue on a long-term, longitudinal basis. They inject a paramagnetic probe into the tissue to measure the oxygen at a baseline level and throughout treatment. In the rat model, they “irradiate a portion of the log” and monitor the oxygen levels. So far, the levels drop in the first two weeks after irradiation “and then slowly come up” in the three to six weeks after.
The team is looking to use the results from this grant to provide preliminary data to apply for other grants to move the research to a human model. “It’s going well,” Dr. Chen said. “We are set up to move to the next phase. That’s a big hurdle.”
Johns Hopkins has a long history of sleep research, but few studies have focused on children. Dr. Ishman’s research into persistent pediatric sleep apnea uses a novel flow sensor, developed by colleague Hartmut Schneider, MD, PhD, to measure the flow of oxygen during sleep.
The grant has helped “solidify” her mentorship relationships at Hopkins. “I worked with them to put the grant together, and it was a great place to start what I hope will be a long collaboration with my adult sleep colleagues,” she said. “The second thing is just dollars and sense. I’ve been afforded more time to spend on trying to develop the program and help work on an infrastructure, so that recruiting additional patients in the future will be easier.”
Dr. Ishman is a bit behind on her goal of enrolling 27 patients into the sleep study, in part because of delays in getting the sensors and the lack of a research assistant. Still, the grant has helped her move the project toward her long-term goal: a risk-reward algorithm.
“I’m hoping, if we can differentiate patterns of flow signal, it will give us a better feeling for whether or not people are good candidates for tonsillectomy and adenoidectomy therapy,” she said. “For example, if you are somebody who has complete apneas, are you in fact not as good a candidate for us to consider tonsil and adenoid removal as someone who has partial flow obstruction?” She said such a distinction is more of a concern in children who have neurological impairment or anatomical abnormalities than in children with no such impairments or abnormalities. Her research, she said, may help physicians decide the best primary therapy for children with Down syndrome, cerebral palsy or other neurological impairments.
Dr. Parham and his team are looking at a well-studied disease from a new angle. And, based on preliminary results, their human tissue culture model exploring the effects of bisphosphonates on otosclerotic osteoblasts is showing positive results.
“We know otosclerosis as a disease of hearing, but it’s really a disease of the bone,” Dr. Parham said. “Therefore, to better understand it, we should be studying the diseased bone.”
Dr. Parham and his team are focusing on osteoblast characteristics and their role in otosclerosis. He’s begun treating otosclerotic osteoblast cultures with bisphosphonates, and “lo and behold, they normalized their behaviors.” Their study, he said, confirms that the culture model can reproduce some disease characteristics of otosclerosis, suggesting that the approach can be practical and that those disease characteristics can be normalized with medical therapies.
“This adds additional fuel to the argument that there can be a medical therapy as an adjunct or, perhaps one day, replacement for surgical replacement,” he said. “Our hope is that, in the long term, medical therapies in treatment of otosclerosis will take a greater foothold in the otolaryngology community.”
Dr. Parham is also leveraging his grant to expand his research horizons. He is actively involved in conducting age-related hearing loss and ototoxicity research, clinical trials on the association between osteoporosis and benign paroxysmal positional vertigo and another trial on screening for head and neck cancers using narrow band imaging.
“The Triological [Society] award has been very instrumental in allowing me to pursue all of my research activities and guide them toward maturation,” he said.
A self-described “techie” with a keen interest in miniaturization and robotics, Dr. Zanation hopes to improve quality of life in patients who undergo skull-based tumor surgery by saving the brain from manipulation and damage during surgery.
“People think that the primary advantage of taking tumors out through the nose is the fact that there is no incision on the face or the head. While I agree that is an advantage, I don’t think it’s the primary advantage,” he said. “I think the primary advantage is that you are not moving the brain or the neurovascular structure.”
Dr. Zanation is building a database of information outside of what is traditionally collected in a medical record: sense of smell, sense of vision, sinus function and so on. To do so, his team administers one pre-operative test battery and three post-operative tests.
“If someday we are ever going to be able to compare outcomes between doing operations via the standard approaches or via endoscopic or minimally invasive approaches, we have to have prospective data to compare those things,” he said.
Dr. Zanation’s funding helped him enroll 50 patients in the pilot study, on 40 of whom his team has completed metric time points, and he said they are “pretty close” to analyzing the first subset of data. “We are hoping to apply for a larger project in the next year,” he said, adding that his ultimate goal is to identify the advantages and disadvantages of endoscopic, skull-based surgery.
CAREER SCIENTISTS DEVELOPMENT AWARD
Dr. Kim was awarded an NIH grant in 2008 for just under $680,000, but his Career Scientist Development Award was the perfect supplement to guarantee him the time to research how effective combinational immunotherapy can be in fighting cancer.
“Doing the experiments, even with the help of therapists and other foundation grants … that requires time,” he said. The Triological grant pays for “time I can dedicate to this research rather than seeing patients. That was instrumental.”
After successfully showing slowed tumor growth in mice, Dr. Kim is now working to show how toll-like receptor (TLR) agonists can be used as tumor cell vaccine adjuvants. His research has taught him that simply combining the agonists and the vaccine isn’t enough. He and his team have worked on formulating the biologic engineering required to get the vaccine to absorb the adjuvants. Also, because the formula is not as simple as one agonist for one vaccine, Dr. Kim and his colleagues are working on seemingly countless possibilities for different agonist combinations.
Although all his tests have been on animals to date, Dr. Kim said he is about a year away from beginning patient tests. Specifically, he is looking to pair his science with a colleague’s GVAX for melanoma. Of course, he has his eye on similar vaccines for other cancers, including squamous cell carcinoma, but the holders of some vaccines are companies, and the approval process to formalize those partnerships can take time.
And Dr. Kim is eager to get to work.
“What are the key adjuvants that are important to make tumor vaccines, cancer vaccines work?” he said. “We have decades of experience with multiple labs trying to target tumor antigens, and they clearly have not worked by themselves.”
Dr. Kupferman was the only Clinical Scientist Development Award winner from 2010 in the first year of the grant. His research is focused on how neurotrophin receptors impact the progression of head and neck cancers, particularly oral cancers. He originally received an NIH grant in 2009 that will provide more than $525,000 over five years. His new grant is $80,000 per year for four years.
“We currently use a ‘one size fits all’ approach to treating these cancers … gleaning insights from how these tumors are behaving based on a particular molecular profile may give us insight in how to individualize treatment,” Dr. Kupferman said.
Dr. Kupferman is now hopeful his current funding is just a first step toward a larger proposal he’s drafting. His team has begun looking not just at tumor cells, but also at the surrounding support cells, which he dubs “the neighborhood within which the tumor lives.” He is hopeful a future NIH grant will fund deeper research down that path.
“The grant money from the [ACS and Triological Society] has really given us a boost with which we can now move our research along at a faster pace, ” he said.
Time is money, and Dr. Kim believes the money he received over the past three years has bought him the time to find novel ways to fight head and neck cancer. The project, originally backed by a $400,000 NIH grant award in 2008, targets both epidermal growth factor receptor and vascular endothelial growth factor receptor in oral squamous cell carcinoma, specifically studying how the use of both agents could help improve treatment. The goal is to help reduce the mortality rate of the disease, which Dr. Kim says has remained stagnant at roughly 50 percent for more than three decades.
Dr. Kim, in the third year of his five-year grant period, is becoming a subject matter expert in angiogenesis, particularly in its use as a therapeutic target. “This isn’t esoteric,” he said. “It has real translational impact on the care of our patients and how they are treated.”
The value of multi-year grant funding for his project, Dr. Kim said, can’t be overstated, noting that “a study like this is not something you complete in a year or two.” Physicians looking to tackle long-term research goals need to know there is a financial backstop that enables their work to translate from a laboratory setting to clinical application, he said.
The funding “was very significant because it freed me up from some of my clinical responsibilities so I could dedicate a larger chunk of time toward my research,” he said. ENT TODAY