Government researchers develop stroke vaccine

? Researchers at the National Institutes of Health have developed the first vaccine designed to prevent strokes, and human trials of the novel therapy could begin this summer.

Already the vaccine has shown impressive results when used in rats.

If a similar success is found in humans, it could be a major step toward preventing a disease that is the third-leading cause of death and the leading cause of disability in the United States.

“We’ve been working on this for several years,” said John Hallenbeck, chief of the stroke branch of the National Institute of Neurological Disorders and Stroke.

The therapy involves the use of a nasal spray to administer a protein known as E-selectin. E-selectin is a molecule found in the endothelium, the delicate layer of cells that make up the inner walls of blood vessels.

In rats, repeated exposure to E-selectin slowed the rate at which certain white blood cells migrated to the endothelium, which causes inflammation and leads to clotting.

A stroke occurs when a clot forms in a blood vessel leading to the brain, cutting off blood supply and causing tissue death in the brain. This can happen when there is a buildup of plaque on blood vessels, leading to a tiny rupture at a specific location and a clot that blocks blood flow to the brain.

About 600,000 strokes, one every 53 seconds, occur each year in the United States, according to the American Stroke Assn.

‘Reverse’ vaccine

Although the new approach is considered a stroke vaccine, it actually works in reverse of the way a typical vaccine works. Instead of strengthening the immune system to fight an invading germ, it tones it down to accept certain antigens.

The action is similar to what happens when someone gets an allergy or hay-fever injection.

“People who are more prone to stroke may have vessels that become more activated (inflamed) periodically,” Hallenbeck said. The high-risk group includes people with diabetes, high blood pressure, smokers and older people.

Success in using a vaccine to prevent strokes in rats is no guarantee that the approach will work in people. Over the years, many therapies that showed promise in animals failed to work on people.

Limited success

So far, preventive therapies, including the use of aspirin and drugs to prevent clotting and coagulation, have limited effectiveness in preventing strokes.

Other NIH research has shown that powerful clot-busting drugs administered in a hospital can minimize the damage from a stroke, but there’s a catch: The drugs have to be given within three hours on the onset of symptoms. Less than 5 percent of those who experience a stroke recognize the symptoms soon enough to reach the hospital in time.

In addition, not all hospitals are equipped to administer the drugs.

Trial approval sought

The E-selectin human trials, which still need final approval from the Food and Drug Administration, will test whether an initial dose and several boosters of E-selectin can cause immune tolerance to E-selectin and an increase in cells that produce anti-inflammatory substances.

Whether a blood vessel flows normally or clots is determined locally, within a small segment of any vessel.

By delivering a dose of E-selectin and several boosters, immune cells called lymphocytes can be programmed to become mobile monitors of what is happening on the inner lining of blood vessels.

When a vessel starts to become inflamed, a sign that the immune system is getting too active, lymphocytes will recognize it and react by releasing an agent that suppresses the immune response.

“It sort of deactivates the vessel so it is not likely to clot,” Hallenbeck said.

So far, the approach has been tried only on rats that are genetically prone to strokes.

However, the results have been dramatic. There were 16 to 29 times more strokes in the untreated rats than in the rats that got optimal E-selectin therapy.

“There were not only many fewer strokes, but they were much smaller,” Hallenbeck said.

With final FDA approval, a phase one trial involving 20 to 60 people could start this summer, said Robin Robinson, directors of vaccines at Novavax Inc., a Maryland biopharmaceutical company.

In December, NIH entered into a research and development agreement with a Novavax Inc to test whether E-selectin therapy in people can bring about the immune system responses that could prevent strokes.

If the treatment proves safe and it induces the proper immune response, a larger phase two trial could take place next year.