One approach to treating Rett Syndrome is to identify existing drugs that improve any of the symptoms. The advantage of this approach is that any drug found to be helpful can be fast-tracked to clinical trials, bypassing the many years involved in drug development.

Andrew Pieper, M.D., Ph.D.

RSRT funded investigator Andrew Pieper, M.D., Ph.D. at the University of Texas Southwestern Medical Center in Dallas is currently screening drugs of interest in the Rett knockout mice.

The idea for the Rett screen came from a bold project begun a handful of years ago in the lab of RSRT Scientific Advisory Board member, Steve McKnight and Pieper who was, at the time, a post-doc in the lab. The goal of the screen was to identify compounds able to enhance the production of neurons. The laborious and risky project has yielded a compound, called P7C3, which protects newly created neurons and improves learning and memory. The study was published last week in the high profile journal, Cell.
We congratulate Drs. McKnight and Pieper and hope for similar results in the ongoing Rett screen.

Small molecule boosts production of brain cells, protects new cells from dying

DALLAS – July 8, 2010 – UT Southwestern Medical Center researchers have found a compound that preserves newly created brain cells and boosts learning and memory in an animal study.

The study of this compound, which appears in the July 9 issue of Cell, springs from a $2.5 million National Institutes of Health Director’s Pioneer Award to Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study.

Over a three-year period, the research team led by Dr. McKnight and Dr. Andrew Pieper, assistant professor of psychiatry and biochemistry at UT Southwestern, screened 1,000 individual molecules to see which ones might enhance the production of neurons in the adult mouse hippocampus, a region of the brain critical to learning and memory. The scientists found that one of the compounds, called P7C3, achieved this by protecting newborn neurons from dying.

The researchers then administered P7C3 to “knockout” mice lacking a gene that controls the generation of new neurons in the hippocampus. Humans who lack this gene have a variety of learning disabilities, and the “knockout” rodents show related abnormalities as well as a poorly formed hippocampus. When the “knockout” mouse received P7C3, however, normal structure and function of the hippocampus were restored.

In elderly rats, which characteristically show a decline in the birth and formation of hippocampal neurons, the researchers found that P7C3 increased both the birth and survival of new neurons, and the memory and learning capability of the aged rats.

“It’s been a wonderful experience,” Dr. Pieper said. “At first there was a lot of doubt, because we could have gone through the whole screen and found nothing.”

The researchers currently are studying the mechanism by which P7C3 protects cells from dying, and whether it might have any protective effect in other models of neurodegenerative disease.

“We don’t know yet whether P7C3 can block the death of mature nerve cells, which is what occurs in humans with these conditions,” Dr. McKnight said.

Dr. McKnight was one of the first 12 recipients of the NIH Director’s Pioneer Award, which is designed to allow researchers to pursue risky experiments that have the potential for producing highly innovative results.

“When I received the award, I thought ‘I’m not going to waste it on something safe – I’m going to go for it. That’s what the NIH expected of me and my team,'” Dr. McKnight said. “I’d like to give the NIH credit for betting on ‘cowboy’ science. If this pans out, it will be the most useful contribution of my career.”

Dr. Francis Collins, director of the NIH, said Dr. McKnight’s results exactly fit the award’s purpose.

“The NIH Director’s Pioneer Award gives highly innovative investigators the freedom to pursue bold new avenues of research. Such approaches can yield substantial payoffs, as in the case of the exciting clinical implications of Professor McKnight’s basic neurobiological research discovery,” Dr. Collins said.

Other press releases on this discovery

Mental decline thwarted in aging rats
A chemical to make brain cells grow