Know Your Madisonian: Waisman Center director focuses on Alexander disease

July 07--Albee Messing is director of UW-Madison's Waisman Center, a hub of nearly 60 faculty members who do biological and behavioral research on conditions such as autism, Down syndrome and Parkinson's disease.

The center has 11 clinics and a preschool that includes children with developmental disabilities.

Messing, 65, of Madison, focuses on Alexander disease, a rare and usually fatal disorder of the nervous system. Only about 500 cases have been reported since it was discovered in 1949.

He is married to Marsha Mailick, vice chancellor for research and graduate education and former director of the Waisman Center. They have four adult children and three grandchildren.

What is the Waisman Center?

It is a multidisciplinary center dedicated to research, clinical service and education in the field of intellectual and developmental disabilities. We're part of a network of such centers around the country, funded by the National Institutes of Health, that dates back to an initiative in the early years of the Kennedy administration.

When and how was the center founded?

It began with a new institute at the NIH, the National Institute of Child Health and Human Development. Laboratories were initiated around 1963. Harry Waisman spearheaded the effort from Wisconsin. A celebration of the opening of the laboratory here prompted a congratulatory telegram from President John F. Kennedy, which was sent Nov. 20, 1963, two days before he went to Dallas (and was assassinated). The center building (near UW Hospital) opened in 1973.

Why were the Kennedys interested in this type of research?

Rosemary Kennedy, one of JFK's sisters, had an intellectual disability and was institutionalized in Wisconsin (at St. Coletta in Jefferson). She was subjected to a lobotomy and was clearly impaired after that. There may have been a mixture of personal and political interests that coalesced around wanting to take the initiative in helping people with some type of disadvantage, and they chose the area of mental retardation.

Why do you study Alexander disease? It was never my intent. I went to the University of Pennsylvania, in a program that combined veterinary school and graduate school. I had a general interest in understanding the cell biology of diseases, especially the nervous system. After coming to Madison in 1985, I started working on a particular cell, called an astrocyte, and a particular gene expressed in astrocytes, called GFAP. We created mice that had no GFAP or too much GFAP. Around 1995, we realized that in mice with too much GFAP, the astrocytes not only got bigger, but they formed distinctive structures called Rosenthal fibers.

There's one condition where the brain is full of Rosenthal fibers: Alexander disease. Most neuropathologists never see a case, but they all learn about it. It was suspected of being genetic in origin, but nobody had any idea where the gene was. We proposed GFAP as a candidate gene. We collected samples from 13 patients; 12 had mutations in this gene. We reported that in 2001. Patients who had gone from doctor to doctor for a diagnosis now had a simple blood test.

Do you think there will be a treatment someday?

I have no doubt about that. In 2005, I started screening FDA-approved drugs to see if they'd reduce the production of the protein. We found drugs that reduced it a little bit, but not very much, and they all had side effects. There have been new developments in a different technique for suppressing gene expression, called antisense. In mice, we can shut down GFAP expression and reverse many features of the disease. I'm working with a company to develop treatments, but we're not even up to the point of doing a clinical trial. It will be a huge hurdle to actually cure Alexander disease. For now, our goal is to convert a lethal condition into a chronic disease, which would be a big step.

What does the public misunderstand most about science?

They don't understand ambiguity. There's a lot of uncertainty about how we design and interpret experiments. It's what we do all the time, to try to understand the source of all that variation. On the other side, people exploit disagreements among scientists for their own political purposes and exaggerate it.

-- Interview by David Wahlberg

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