A UCSF and Gladstone Institutes team discovered a pair of cancer drugs that successfully treated a model of severe Alzheimer’s disease. From left: Marina Sirota, PhD; Yaqiao Li, PhD; and Yadong Huang, MD, PhD. Photo by Michael Short/Gladstone Institutes
Scientists at UC San Francisco and Gladstone Institutes have identified cancer drugs that promise to reverse the changes that occur in the brain during Alzheimer’s, potentially slowing or even reversing its symptoms.
The study first analyzed how Alzheimer’s disease altered gene expression, the activity of genes in a cell, in single cells in the human brain. Then, researchers looked for existing drugs that were already approved by the Food and Drug Administration (FDA) and cause the opposite changes to gene expression.
They were looking specifically for drugs that would reverse the gene expression changes in neurons and in other types of brain cells called glia, all of which are damaged or altered in Alzheimer’s disease. Next, the researchers analyzed millions of electronic medical records to show that patients who took some of these drugs as part of their treatment for other conditions were less likely to get Alzheimer’s disease.
When they tested a combination of the two top drugs — both of which are cancer medications — in a mouse model of Alzheimer’s, it reduced brain degeneration in the mice, and even restored their ability to remember.
“Alzheimer’s disease comes with complex changes to the brain, which has made it tough to study and treat, but our computational tools opened up the possibility of tackling the complexity directly,” said Marina Sirota, PhD, the interim director of the UCSF Bakar Computational Health Sciences Institute, professor of pediatrics, and co-senior author of the paper. “We’re excited that our computational approach led us to a potential combination therapy for Alzheimer’s based on existing FDA-approved medications.”
The findings appeared in Cell on July 21. The research was funded in part by the National Institutes of Health (NIH) and the National Science Foundation.