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Last updated on April 16, 2014 at 17:29 EDT

Nasal Spray May Treat Alzheimer’s

February 4, 2008

A nasal spray that could treat Alzheimer’s disease — a dream more than two decades in the making for one Twin Cities researcher — is getting more attention these days.

Several studies are using the nose-to-brain method of delivering drugs that was invented in the late 1980s and patented by William Frey II, director of an Alzheimer’s research center at Regions Hospital in St. Paul. Last month, researchers in Washington state reported using intranasal insulin to improve memory and attention for patients with early-stage Alzheimer’s.

The study is the latest support for Frey’s basic discovery — that drugs targeted at nerve endings in the upper portion of the nose can rush to the brain and bypass the protective blood-brain barrier.

Whether it’s the secret to beating Alzheimer’s is unclear. Doctors and scientists have proposed dietary changes, vitamin supplements, stem cell therapies and vaccines to prevent or treat the now-incurable disease. Frey’s work at least gives hope against a disease that is the seventh-leading cause of death in the U.S.

The nose-to-brain discovery was so simple that Frey spent years convincing officials at the U.S. Patent Office that it was a useful method of drug delivery. Then he spent several more years convincing them that it was an actual discovery and not just a feature of anatomy.

“Some people would say it’s as simple as the nose on your face — that everybody already knew that,” Frey said. “But the truth of the matter

is, no, nobody knew it.”

AVOIDING THE BLOCKADE

Most nasal sprays are directed to the lower part of the nose so medication can quickly enter the bloodstream. Drugs to treat neurological conditions don’t work through this route, though, because of the protective blood-brain barrier.

While this blockade of cells and blood vessels protects the brain and spinal chord from harmful organisms, it also keeps out most drugs and has stymied otherwise promising therapies.

Avoiding this barrier is what makes intranasal delivery “a potentially powerful therapeutic tool,” according to the Washington research group. Its study was small, with 24 patients receiving daily insulin or a placebo, but the results, published in the journal Neurology, were persuasive.

Patients taking intranasal insulin were mentally sharper, and their blood sugar levels remained healthy.

Several companies have made nasal spray devices that can target this nose route to the brain, but it’s unclear if any drugs will take advantage of it.

Frey recently gained federal funding to study the intranasal delivery of deferoximine, a generic drug that removes toxic amounts of iron and other metals from the body. One theory about Alzheimer’s is that excess metals in the brain cause oxidation and damage to the neurons — the brain’s thinking cells.

Canadian company Allon Therapeutics is in the second phase of U.S. clinical trials with an experimental drug that may support the growth and repair of brain cells. The intranasal drug is being evaluated as a treatment for Alzheimer’s and schizophrenia.

Insulin might hold the most immediate promise, given that insulin injections have been used safely for years to treat diabetes. There is building research, including the Washington study, that insulin plays a crucial role in Alzheimer’s and other diseases that erode memory and thinking skills.

“The brain needs insulin to help brain cells take up blood sugar,” Frey said. “It gives them the energy they need so you can think and remember.”

COMPANY NOT INTERESTED

A drug company’s disinterest could slow the development of this potential therapy. Chiron, a subsidiary of Novartis, holds patents for the intranasal delivery of insulin and drugs that mimic insulin. (Both patents were sold to the drug company by HealthPartners — the health system that owns Regions — and still list Frey as the inventor.)

When asked if Novartis is developing the ideas in these patents, a spokesman replied, “We’re not.”

It’s disappointing to Frey and other believers. The idea offers limited financial returns for Novartis, because it doesn’t involve the development of a new drug the company could provide exclusively to the market.

Still, it’s an untapped market. Few therapies exist for the estimated 5.1 million Americans with Alzheimer’s. A primary drug is Aricept, which slows the degeneration caused by Alzheimer’s but doesn’t halt or reverse the disease.

Drug companies are studying other Alzheimer’s treatments, and research institutions are finding more apparent targets in the brain.

Researchers at the University of Minnesota, for example, have discovered a unique cluster of proteins in mice that is connected to memory loss. They suspect drugs could prevent this cluster from forming in human brains, which could prevent or treat Alzheimer’s.

Frey doesn’t know whether his research could end up targeting symptoms of Alzheimer’s or whether it could cure the disease altogether. Drug companies are interested in his findings, and he is meeting with them in the coming weeks.

He spent last week in California at a lab that will help conduct the studies with deferoximine, the iron-reducing drug. The goal is to study in animals whether intranasal use of that drug is safe.

If safety is proven, Frey said, he could start to pursue human clinical trials by the end of the year.