Of mice and humans
The Nature paper represents 14 years spent pursuing a rigorous research strategy: Replicate the disease in an animal, identify molecules present in animals with the disease and absent in those without it, isolate the molecules, and see if they cause the disease in healthy animals.
"Dr. Ashe's paper is the quintessential demonstration of this strategy," says Timothy Ebner, M.D., Ph.D., head of the University's Department of Neuro-science and holder of the Maurice Visscher Land-Grant Chair in Physiology. "You really have to attack this disease at the basic level — to understand it at the molecular level. Then you have a real chance to intervene."
Researchers involved in the study include: (front) Karen Hsiao Ashe, Dina Nash, Colleen Forster, Lisa Kemper, and Matt Sherman; (middle) Preethi Krishnan, Linda Kotilinek, Sarah Chevaillier, Pauline Sharpe, and Jen Paulson; (back) Carol Ma, Sylvain Lesné, and Martin Ramsden.
Although the paper marks a critical milestone, a wide gap remains between a memory-impairing molecule in a mouse model and a prescription at a local pharmacy. The University aims to bridge that gap with the newly formed Center for Memory Research and Care. Under Ashe's direction, the center will have three components: basic research, translational research, and clinical research and care.
The next steps in basic research include an investigation of autopsied brain tissues from people with and without memory impairment to determine if Aß* can be identified, quantified, and correlated with the individual's degree of impairment. Ashe will coordinate this work with David A. Bennett, M.D., the primary investigator of the Religious Orders Study at Rush University Medical Center in Chicago.
Translational research will focus on developing compounds able to block the formation of Aß*, break it down, or interfere with its ability to affect brain cells. Ashe hopes to collaborate on this effort with Gunda Georg, Ph.D., who was recently recruited from the University of Kansas to lead the College of Pharmacy's Department of Medicinal Chemistry.