People who suffer from the repeated headaches, facial swelling, and blocked breathing passages of chronic rhino-sinusitis know that the pain isn’t limited to the physical. Adding to their suffering is the knowledge that there are no treatments that could forestall the endless cycle of symptoms. Many who fall victim to the most extreme type of sinusitis benefit only temporarily from surgery, while steroids such as prednisone can help with symptoms but carry serious side effects. Scientists have searched in vain for decades for ways to provide long-lasting relief to sinusitis patients, who spend more than $1 billion per year on a drugstore-aisle’s worth of remedies that may quiet their symptoms for a scant few hours.
Now, a group of researchers at the Johns Hopkins Allergy and Asthma Center led by Jean Kim, assistant professor of otolaryngology and allergy and clinical immunology at the School of Medicine, believes it may have identified the culprit behind the most severe form of the disease. The discovery of the protein responsible for triggering unwanted growths inside sinuses may lead, they hope, to drug treatments that could halt their development.
Since 1996, Kim and her team have gathered tissue and other samples from their patients at the Allergy Center at Johns Hopkins Bayview Medical Center. There has been no shortage of subjects, there or elsewhere across the country. One in six people in the United States experiences sinusitis—the most common respiratory complaint—a condition that is more debilitating than the common cold, is often accompanied by infections, and regularly recurs. About one-third of sinusitis sufferers will also develop a form of the disease that causes polyps—overgrowths of tissue that block airways and increase the risk of infection. The polyps can be removed during surgery, but almost always grow back.
The Hopkins team studied cells taken from inside the noses of patients with polyps, and then tested them to see how they grew. They noticed those cells grew two and a half times faster than ones taken from a control group of people who were free of sinus disease. As part of their search for why this was so, researchers had patients rinse their sinus passages with a solution, and then tested the resulting rinse mix for various growth factors. They discovered that a protein called vascular endolethial growth factor, or VEGF, which is important for normal blood vessel development, was found in much higher quantities in samples taken from patients with polyps. Researchers also found elevated levels of VEGF in the sinus polyp tissue taken from patients during surgery.
Tests in Petri dishes confirmed the findings. The more VEGF that was found in a culture, the faster cells grew. To see if they could slow down growth, they introduced anti-VEGF antibodies to the cultures. Such agents are already being used in remedies for certain types of breast, kidney, and prostate cancers, and as a treatment for cell overgrowth in the eye that accompanies macular degeneration. The anti-VEGF antibodies slowed the rate of growth of cells to that of non-sinus patients’ cells. The results were published in the December 1 issue of the American Journal of Respiratory and Critical Care Medicine.
“We’ve found that our theory works in a model of a human system,” says Kim. “Next, we have to show that the idea will work in a human being.”
Besides offering hope for a possible treatment, the Hopkins study could also lead to a new way to diagnose and track the disease. Instead of putting patients through repeated CT scans that bombard the head with radiation, physicians might one day use sinus “stains” that detect levels of VEGF to monitor a patient’s degree of disease, or to find polyps early on that might evade detection during a physical examination, Kim says.
“We need to do more research to see whether anti-VEGF could work as a preventive, or to shrink polyps,” she adds. Her group is now seeking out collaborations with industry to develop a treatment based on the findings. Kim hopes that clinical trials on those agents will be rolled out in the next five years. “It would be great if we could figure several ways to tailor treatments using the anti-VEGFs that could help patients who may have varying levels of disease,” Kim says. Such a remedy would be a boon—and not merely for sinus sufferers. “The cost in negative impact is amazing,” adds Kim. “This disease is very expensive for the health care industry to deal with.”
Photo by David March