A team of neuroscientists and chemists from the U.S. and China today
publish research suggesting that a class of currently used anti-cancer
drugs as well as several previously untested synthetic compounds show
effectiveness in reversing memory loss in two animal models of
Alzheimer's disease.
CSHL Professor Yi Zhong, Ph.D., who led the research conducted in fruit
flies and mice, says he and his colleagues were surprised with their
results, which, he stressed, used two independent experimental
approaches "the results of which clearly converged."
Specifically, the research converged on what Zhong's team suggests is a
"preferred target" for treating memory loss associated with the
amyloid-beta (Aβ) plaques seen in advanced Alzheimer's patients. That
target is the epidermal growth factor receptor, often called by its
acronym, EGFR.
Overexpression of the EGFR is a characteristic feature of certain
cancers, notably a subset of lung cancers. Two targeted treatments,
erlotinib (Tarceva) and gefitinib (Iressa), can dramatically, albeit
transiently, reverse EGFR-positive cancers, by blocking the EGFR
receptor and thus preventing its activation.
The newly published research by Zhong's team suggests that the signaling
within cells that is induced by EGFR activation also plays a role in the
pathology - still poorly understood - involved in Aβ-associated memory
loss seen in Alzheimer's patients.
Zhong's team demonstrated that enhanced activation of EGFRs in brain
cells exacerbated memory loss in the Aβ-42 fruit fly model of
Alzheimer's disease. This led them to dose 3-day-old flies of the same
type with the two anti-cancer EGFR inhibitors over a week's time, which
was shown in behavioral tests on day 11 to prevent memory loss. The
results were then confirmed in mouse models of Alzheimer's, also based
on the human Aβ-42 gene.