This Nasal Spray May Clear Your Brain, Not Your Sinuses

Medically Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
From the WebMD Archives

Feb. 22, 2001 (Ft. Lauderdale) -- If you've seen the Oscar-nominated film Traffic, you've seen actors mimic the rush that comes from snorting a drug. That "rush," says a Minnesota brain researcher, happens because the drug catches a ride on the nerve highway to the brain, so it reaches pleasure centers in the brain even before it can be detected in the bloodstream.

The researcher says this same nonstop nerve highway can deliver healing drugs directly to the brain, and that simple proposal could someday revolutionize the treatment of stroke or Alzheimer's and Parkinson's diseases.

William H. Frey II, PhD, explains that the nose contains nerve endings connected directly to two very powerful networks: the olfactory nerves, which control the sense of smell, and the trigeminal nerve, which sends sensations from the face and head to the brain.

Those nerves, Frey tells WebMD, provide a "direct shot from the nose to the brain," without stopping first in the bloodstream. That means that a drug can reach the brain in less than 15 minutes, less than half the time it would take if the drug were injected into a vein.

This is important, says Frey, because drugs that enter the bloodstream are often stopped short before making it to the brain by a natural protection mechanism called the "blood-brain barrier." Many drugs for conditions such as stroke or Alzheimer's disease are promising in animal studies but flop when tested in humans because the drugs never make it past the hurdle of this barrier.

He explains that any drug that was previously considered unable to "make it past the blood-brain barrier can be taken back down from the shelf, dusted off, and tried again with this method."

But, according to several other researchers who met recently at the American Stroke Association's 26th International Stroke Conference, Frey's assessment is very optimistic. Frey did demonstrate the effectiveness of his nasal delivery system in a paper delivered at the conference -- but his demonstration was in rats, not people.

He and his colleagues from the Alzheimer's Research Center of the HealthPartners Research Foundation in Saint Paul, Minn., put a few drops of a natural substance called insulin-like growth factor-1 into the noses of rats that had had a stroke.

Earlier experiments demonstrated that this substance can heal injured rat brains, but it had to be applied directly to the brain. In the past, says Frey, "the only way to get it to the human brain would be to drill a hole in the skull and put it in, so it is not considered a practical treatment for humans."

Within hours of getting the drug, the rats showed signed of brain healing: Swelling was reduced, and movement improved, says Frey.

Philip Gorelick, MD, professor and director of the Center for Stroke Research in Chicago, tells WebMD that "the standard method of delivery for drugs to treat stroke is [via an injection into the vein]. So, if this were true, it would be novel." But after consulting with a number of colleagues who focus their research on animal studies, Gorelick's enthusiasm was dampened.

The other researchers, says Gorelick, weren't that impressed. He says that the method would have to be carefully tested in rats to see if the drug was adequately reaching all the areas in the brain it needed to.

Larry B. Goldstein, MD, a member of the AHA's Stroke Council and an associate professor of medicine at Duke University, says there is a very big difference between the olfactory nerves in rats and olfactory nerves in humans because a much larger part of a rat's brain is dedicated solely to the sense of smell.

Frey agrees that rats have a more developed sense of smell but he adds that the trigeminal nerve, "is proportionally the same size in rats and humans." He says that "trigeminal nerves also hang down into the nasal cavity, and so the drug can just as easily travel along that [nerve] pathway."

Goldstein does, however, agree that a nerve route could provide a speedy pathway to the brain. Speed is important to stroke researchers, whose motto is "Time is brain," meaning that the longer the blood supply to the brain is cut off, the more brain cells are destroyed.

Frey, who says that the idea for the nose drops came to him "in a dream," says he has patented his "Method for Administering Neurologic Agents to the Brain" in the United States and several other countries. He says that more research needs to be done but suggests that he may pursue that research in partnership with a drug company.

And, if you think that nose drops to treat stroke sound like something Dr. McCoy would use on Captain Kirk, what about a laser that takes aim at blood clots deep inside the brain and pulverizes them? That's exactly what a new device called an Endovascular Photo Acoustic Recanalization laser, or EPAR for short, is supposed to do.

Helmi Lutsep, MD, of the Oregon Stroke Center at Oregon Health Sciences University in Portland, is one of several researchers who tested the new laser in a safety trial. Based on that trial, the FDA has given the go-ahead for larger studies.

Lutsep says the new laser, which was tested in 26 stroke patients, is small enough to be used in most blood vessels in the brain. Earlier lasers were too large or inflexible to be used in small vessels, she says.

Goldstein says the EPAR laser is one of several lasers now being tested for what is called "mechanical clot disruption." While the devices are intriguing, he says there is a concern "that mechanical devices may accidentally dislodge other clots," thus causing additional damage while attempting to treat the original stroke.

Another worry is that the devices, which have to be threaded through very tiny vessels using guide wires, may actually tear the delicate walls of blood vessels in the brain. Goldstein says, for example, that Lutsep's group reported three such tears in the 26 patients treated in their safety study. Lutsep says those three patients had no ill effects from the tears, but according to Goldstein, "they were lucky."

Lutsep, however, shrugs off criticism because she says that laser technology is likely to triumph in the end for a very simple reason: time. Once inside the brain, the EPAR laser "can dissolve a clot in 36 seconds," she says, while it takes clot-busting drugs almost an hour," even if you deliver the drug directly to the site of the clot."