Alzheimer's disease: Researchers find two cancer drugs reverse damaged gene behaviour in mice
Alzheimer's disease is an ageing-related disorder in which cognitive function steadily declines, affecting speech and memory, and eventually can interfere with everyday activities.
Scientists at the University of California, San Francisco, and Gladstone Institutes in the US first saw how gene behaviour was affected in Alzheimer's disease in a single brain cell. The researchers then looked at 1,300 drugs approved by the US Food and Drug Administration (FDA) and which of them reversed the damage.
The next stage of the study, published in the journal 'Cell', analysed electronic medical records of about 1.4 million patients and found that patients who took some of these drugs for treating conditions other than Alzheimer's disease were less likely to get the ageing-related neurological disorder.
Testing the top two drug candidates -- 'letrozole' and 'irinotecan', both of which are cancer medications -- in a mouse model having Alzheimer's disease, the researchers found that brain degeneration was reduced and a restored ability to remember.
Letrozole is usually prescribed for treating breast cancer, and irinotecan for colon and lung cancer. The combined effects of two drugs were found to reverse damaged gene behaviour in neurons and glia (a type of brain cells that surround and support neurons).
Further, toxic clumps of proteins and brain degeneration -- hallmark features of Alzheimer's -- were found to be reduced and memory restored, the researchers said. The team added that out of 1,300 drugs, 86 reversed gene behaviour changes in one type of brain cell and 25 reversed them in other types. However, only 10 had been approved for use in humans by the FDA.
"Thanks to all these existing data sources, we went from 1,300 drugs, to 86, to 10, to just five," said lead author Yaqiao Li, a postdoctoral scholar at Gladstone Institutes.
"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 co-senior author Marina Sirota, professor of paediatrics and an interim director at the University of California.
Co-senior author Yadong Huang, director of the center for translational advancement at Gladstone Institutes, said, "Alzheimer's is likely the result of numerous alterations in many genes and proteins that, together, disrupt brain health."
"This makes it very challenging for drug development -- which traditionally produces one drug for a single gene or protein that drives disease," Huang said. The electronic medical records analysed in the study came from the University of California's Health Data Warehouse, which includes anonymised health information on 1.4 million people over the age of 65.
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