By Janni Simner

Biochemist Willliam H. Frey II's research in intranasal drug delivery may promise new treatments for Alzheimer's, stroke, and Parkinson's disease, among others. The method of delivering medicine to the brain, via nose drops, literally came to him in a dream.

As director of HealthPartner's Alzheimer's Research Center at Regions Hospital in St. Paul, Minnesota, William H. Frey II has spent years seeking effective treatments for this disease. But he and his team of biochemical researchers initially faced a barrier—literally, the blood-brain barrier that kept medications they tested from reaching the brain through the bloodstream. When a solution finally presented itself, it came via an unexpected route.

"I dreamt I was arguing with some other scientists," Frey explains. The scientists kept insisting his research could never succeed. "Then, at the end of the dream, an idea came to me. Maybe the way to get [medication] to the brain was by using nose drops." Researchers already knew that harmful viruses could reach the brain through the nasal cavity. "It occurred to me that if bad things could reach the brain this way, maybe we could get something good in there, too."

Someone else might have dismissed the idea upon waking. Frey started writing a patent application—and embarked upon research that may promise new treatments not only for Alzheimer's, but also for other brain-related diseases.

Pursuing unconventional ideas runs in Frey's family. "My mother and father both had a strong sense of faith in their own ideas," Frey says. "They taught that to me."

In fact, family has influenced Frey in many ways, affecting not only his decision to become a research scientist, but also to begin his studies at Washington University.

He comes from a long line of Washington University alumni, including his father, businessman William H. Frey, Sr., B.S.B.A. ’43, LL.B./J.D. ’47; and his grandfather Abraham Frey, A.B. ’10, a St. Louis judge and colleague of William Howard Taft, the former Supreme Court justice and U.S. president, after whom William Frey, Sr. was named. (William Frey II's great-uncle, great-aunt, and great-great-aunt also attended the University.

I heard nothing but wonderful things about Washington University," Frey says. He pursued a bachelor's degree in chemistry and found the praise well-justified. He learned from Nobel laureates and world-renowned politicians, and he discovered a tremendously supportive environment.

It was a great place to get an education. A place focused on learning, research, and excellence, one where how well you do is up to you."

While William Frey, Sr. helped lead him to Washington University, Frey's mother, Brena Feldman Frey, was key to his decision to become a researcher once he was here. Although not a scientist herself, she was a spirited freethinker who "spent a great deal of time searching for answers to questions other people didn't even think to ask. She was always investigating things," Frey says. "When she had ideas, I paid attention."

"If we can demonstrate that intranasal delivery works for treating one brain disease in humans, then it will be much, much easier to develop drugs for Alzheimer's, stroke, Parkinson's disease, and many others," says William Frey. "The main thing is how much this research could benefit families."

After earning a bachelor's degree in chemistry from Washington University in 1969, Frey pursued a Ph.D. in biochemistry at Case Western Reserve University. While he was there, Frey investigated a question his mother had asked him: "Why is it that people cry tears?" He would pursue the answer, alongside his Alzheimer's work, for many years. He took a scientific approach to her inquiry, and he discovered emotional tears were chemically different from other tears. That research resulted in interviews with People magazine, the Today Show, Good Morning America, and others, as well as a book, Crying: The Mystery of Tears (Harper and Row). "Perhaps the reason people feel better after crying is that they're removing chemicals that build up during stress," Frey suggests, adding that the question remains open to further research.

Upon graduating from Case Western, Frey pursued postdoctoral work at the University of Minnesota. There, he was approached by two psychiatrists affiliated with St. Paul's Regions Hospital. They sought someone who could study the brains of Alzheimer's patients from a biochemical perspective.

Learning more about the workings of the brain appealed to Frey. He applied for funding and started the Alzheimer's Research Center at Regions, planning to stay for a year or so. "That was in 1977," he says, "and I'm still at it."

Frey's research team began by focusing on tangles, abnormal proteins that accumulate in the brains of Alzheimer's sufferers. The team came to believe that altered nerve cell microtubules and microtubule-associated proteins were involved in tangle formation. The National Institutes of Health disagreed with this theory and, subsequently, cut off Frey's funding when he would not abandon the idea. Without financial support, Frey was forced to let much of his staff go, but others pursued the research begun at the center. Within a few years, Khalid Iqbal of New York State Institute for Basic Research had used techniques developed by Frey's group to prove their theories correct.

Currently, Frey is working to put his ideas about intranasal drug delivery into practice, experimenting with a class of proteins known as nerve growth factors. In 1997, the center began collaborating with a pharmaceutical company, Chiron Corporation. The results look increasingly promising.

At the International Stroke Conference in February 2001, Frey and Xin-Feng Liu, a researcher at the center, showed that when rats experiencing strokes were given nose drops containing a particular nerve growth factor, the brain damage they suffered decreased by about 70 percent. There is strong cause to hope that these findings will benefit Alzheimer's and other brain-related illnesses as well.

Frey hopes to move to human clinical trials soon. While not yet at liberty to share the details of specific research proposals, he says of future plans: "If we can demonstrate that intranasal delivery works for treating one brain disease in humans, then it will be much, much easier to develop drugs for Alzheimer's, stroke, Parkinson's disease, and many others.

"The main thing is how much this research could benefit families," adds Frey, who lost a grandmother to Alzheimer's in 1985. He regularly receives calls from the families of other Alzheimer's patients, and their stories provide a strong impetus for continuing his research.

Outside of the lab, Frey continues to spend time with his own family, which includes children Brandl, William III, and Benjamin, ages 22, 19, and 15. He also enjoys writing poetry and occasionally teaching tae kwon do.

He remains committed to examining ideas carefully, both his own and those of others. "I think a lot of people have good ideas and dismiss them," Frey says. "They assume that if they really had a good idea, someone else would have already thought of it first.

"But if you have an idea and you want to succeed with it, in business or science or anything else, you have to be persistent. You have to believe in yourself."

Janni Lee Simner, A.B. ’89, is a free-lance writer based in Tucson, Arizona.


For more information on the Alzheimer's Research Center, please call 1-800-229-2872, or visit the Web site:



William H. Frey II comes from a long line of family members, including his father and grandfather, who attended Washington University.