Dr. Fred Finkelman (McDonald Professor of Medicine and Professor of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Veterans Affairs Medical Center and Cincinnati Children’s Hospital Medical Center) has received a FARE research grant for a study that could lead to an innovative treatment for food allergies. We spoke with Dr. Finkelman about his distinguished career and his interest in the field of food allergy.
What led you to choose a career in research?
I grew up in New York City, where my mother was a kindergarten teacher. One of her heroes was Sir Alexander Fleming, the discoverer of penicillin. As a young boy, I loved hearing her tell how this antibiotic developed from his accidentally finding a mold that contaminated a bacterial culture he was growing, killing the bacteria. Rather than fuming about a ruined experiment, Fleming realized the importance of this finding. Hearing that story, I decided that research was the most exciting and rewarding thing one could do in life. I still think so. I particularly love the combination of dividing time between the laboratory – trying to find something new and important, with a high risk of failure, but the possibility of having a huge impact on human health – and the clinic, where every patient visit offers the opportunity to think of a way to help someone live longer and better.
What prompted your interest in food allergy?
As an adolescent, I was treated by an allergist for allergic rhinitis and asthma, and spent a couple of summers working in his lab. Although rheumatology became my clinical specialty, I remained very interested in allergy. My research studies, which focused on immunology, started out being mostly basic, but gradually concentrated more and more on animal models of human disease, especially allergic disorders. Recent studies have stimulated me to learn more about human food allergy and how food allergy develops. Of course, once you begin to study a clinical problem, you get to know people who have that problem, which considerably increases your desire to find a better way to treat the problem.
What is the significance of your research for the development of new treatments for food allergy and other diseases?
The food allergy treatment we are developing in our FARE-funded study is based on “rapid desensitization,” a process allergists use to suppress reactions in patients who are allergic to a drug, but who require that drug for treatment of a disease (for example, penicillin-allergic individuals who need to be treated with penicillin). Patients are given an initial dose of the drug that is too small to cause a problem, and then the dose is increased rapidly over several hours. Most patients become able to tolerate a therapeutic dose of the drug without a problem. To adapt this approach to food allergy, we have developed a unique monoclonal antibody – an antibody grown in the laboratory – that deactivates mast cells, which play a key role in food allergy reactions. In a previous study, we rapidly desensitized mice to food allergens by injecting them with increasingly large doses of this antibody. Now, we will continue our work in mouse models, with the goal of adapting this approach to humans over the next several years.
Some of our other studies also have significance for the diagnosis and therapy of food allergy and other diseases. For example, our research led to an approach that biotechnology and pharmaceutical companies are using to test drugs that may inhibit immune diseases by suppressing the body’s activation of lymphocytes, a type of white blood cell. Our studies of how some types of antibodies can block diseases that are caused by other kinds of antibodies has led to an approach that may be useful in both allergic and rheumatologic diseases, such as arthritis and lupus. Other studies have focused on the role of specific cytokines, which are proteins that coordinate the body’s inflammatory response. These findings have encouraged clinical trials of antibodies that suppress some of these cytokines in allergic diseases, including asthma.
How would you ensure that this potential food allergy treatment is safe? Would it affect your body’s genetic structure or immune system?
This type of therapy is known as a monoclonal antibody, or mAb. Different types of mAbs are already the basis for FDA-approved therapies for many diseases, including cancer, rheumatoid arthritis, multiple sclerosis and Crohn’s disease. Many more are in development.
Monoclonal antibodies are powerful medications that undergo rigorous testing before they become available to patients. The new food allergy treatment we are developing will not change your genetic structure. However, it does redirect the body’s immune response by targeting specific cells responsible for food allergy reactions. In our previous studies, the treatment proved effective in mice, with no obvious side effects. However, this therapy is still in the early stages of development and we need to complete more studies in animal models before we can begin testing in humans. While this additional work may take as long as five years, it is essential, because something that is safe and effective in mice might not be safe and effective in people.
If the FDA gives us the go-ahead for human studies, they will first be done in very small numbers of patients. All clinical trial participants will meet very specific criteria and will be monitored with great care. Before the treatment can be widely available, we will have to answer many questions, including whether it leads to tolerance, which patients are most likely to benefit from it, what short- and long-term side effects it may have, how it compares to other food allergy treatments that might be available by the time it undergoes final FDA review, and more. [Ed. note: FARE will provide updates on the progress of this important research.]
You have received significant funding from the NIH, including a grant that complements your current FARE study. What role does FARE play in advancing researchers’ work?
Most obviously, the possibility of FARE funding encourages researchers to devote their efforts to food allergy research, rather than to a different area. Secondly, by publicizing the results of research, FARE advances the field and convinces researchers that their efforts in this area are likely to be productive. Thirdly, funding from FARE provides the means to do the research. Even when NIH funding is available (and only about 10 percent of NIH grant proposals are funded these days), FARE funding allows investigators to move more rapidly and assuredly. Fourthly, FARE is willing to fund a wide range of studies, including human trials that are therapy-centered, while the NIH tends to favor more mechanistic studies. Funding from both sources allows us to pursue parallel approaches that are likely to advance our understanding how food allergy works and our efforts to develop pharmaceuticals that can safely and rapidly suppress it. Finally, progress is most rapid when researchers collaborate. FARE is providing a community for food allergy researchers, where they can share ideas and their unique expertise.
Why is mentoring young investigators important, and what role might FARE play in helping attract them to the field?
Young investigators provide both continuity and the fresh ideas that are necessary to continue research progress. They want a career path that provides excitement, a feeling of accomplishment and some degree of security. By providing a source of funding at every career stage, as well as a venue where junior and senior researchers who have similar and complementary interests can meet (in person or online), FARE helps promote the entry and retention of young researchers in the food allergy field.