MS Researchers Win $1.7 Million to Study 'Killer' Cells

CINCINNATI—Researchers at the University of Cincinnati (UC) will use a five-year, $1.7 million grant to determine if natural killer (NK) cells, a first line of defense against infection, also provide protection against multiple sclerosis (MS) and related chronic inflammation.

The National Institute of Neurological Disorders and Stroke (NINDS) awarded the grant to Bibiana Bielekova, MD, UC associate professor of neurology and director of the Waddell Center for Multiple Sclerosis.

MS is an auto-immune disease, occurring when the body’s own natural defense system starts attacking the myelin sheath (outer lining) of nerves and neurons.

Many scientists studying MS are focused on the action of T-cells. When the body suffers an infection, these immune-system cells are activated to fight off the biological assault. In MS, scientists believe T-cells turn against the body as they would an infection. Additionally, some scientists believe that MS may be triggered or exacerbated by viral infections.

Over the past few years, however, a small number of researchers have shifted their focus to NK cells. NK cells were discovered more than 30 years ago as a defense against tumors and infections, especially those that are caused by viruses.

“If you look at the immune response like a battle, NK cells would be considered the ‘front line’ of defense,” says Bielekova. “Infection meets NK cells first, and if these killer cells can fight infection on the spot, the secondary army of T-cells isn’t needed. In fact, we’ve found that activated NK cells can actually ‘silence’ T-cells. ”

But if NK cells are deficient or not functioning properly, they don’t provide enough protection and T-cells are activated—and in some cases, over-activated.

Patients with MS often have defects in the number or function of NK cells in their body.

“We aren’t sure if NK cell deficiencies in MS cause the disease, or if the disease causes the deficiencies,” says Bielekova. “But we do know that the medications out there that successfully alleviate MS symptoms have been found, in essence by accident, to improve NK cell activity.”

In March 2006, Bielekova and colleagues published results of a National Institutes of Health (NIH)-funded study on the MS drug daclizumab (Zenapax). The team believed that the drug was working by inhibiting the activation of T-cells.

The group monitored T-cell function in patients who were injected with the drug, expecting to see that the drug inhibited T-cell function.

“But we didn’t see that at all,” says Bielekova. “To our surprise the T-cells were functioning normally.”

But something unexpected was happening: as the numbers of T-cells circulating in the blood of patients taking daclizumab declined by about 10 percent, the number of NK cells increased.

“Not only did the number of regulatory NK cells increase in patients treated with daclizumab,” says Bielekova, “but that expansion correlated with the treatment outcome—the more these cells expanded, the better the MS patients did during the trial. And the longer the patients were on the therapy, the more regulatory NK cells they had and the better they responded to treatment.

“Our ultimate goal now is to understand how NK cells work in the immune response and create more tolerable therapeutics that boost their regulatory action.”

The NIH applied for two patents related to Bielekova’s earlier work on daclizumab. Both patents have been bought by drug companies. Bielekova receives patent royalty payments from the NIH.

Bielekova is among the many clinicians featured at MS Symposium 2007: Education, Support and Solutions, a free event for patients, caregivers and health care providers. The symposium—held Saturday, Oct. 6, at the Oasis Conference Center in Loveland—offers two different educational tracks targeted to patients, a third track targeted to caregivers, and a provider track that offers continuing medical education (CME) credits to neurologists, radiologists, emergency medicine physicians, ophthalmologists, nurses, physical therapists, occupational therapists, social workers and others who work with MS patients.

Registration opens at 8:15 a.m., and the first presentation begins at 9 a.m. Walk-ins are welcome. Patients and caregivers wanting reservation information for the symposium can contact Rebekah Schraer at (513) 769-4400 or rebekah.schraer@ohg.nmss.org. For CME credit information, contact Kimberly DiPilla at (513) 558-6503 or kimberly.dipilla@uc.edu.

The Waddell Center is an affiliate of UC Physicians and part of the Neuroscience Institute—a collaborative involving nine UC College of Medicine academic departments, University Hospital and independent physician practice groups. The institute is dedicated to patient care, research, education and the development of new medical technologies.