Cancer chemotherapy drug reverses Alzheimer's symptoms in mice

Date:
October 5, 2021
Source:
University of British Columbia
Summary:
A drug commonly used to treat cancer can restore memory and
cognitive function in mice that display symptoms of Alzheimer's
disease, new research has found. The drug, Axitinib, inhibits growth
of new blood vessels in the brain -- a feature shared by both
cancer tumors and Alzheimer's disease. This hallmark represents
a new target for Alzheimer's therapies. Mice that underwent the
therapy not only exhibited a reduction in blood vessels and other
Alzheimer's markers in their brains, they also performed remarkably
well in tests designed to measure learning and memory.



FULL STORY ==========================================================================
A drug commonly used to treat cancer can restore memory and cognitive
function in mice that display symptoms of Alzheimer's disease, new UBC
research has found.


==========================================================================
The drug, Axitinib, inhibits the growth of new blood vessels in the
brain -- a feature shared by both cancer tumours and Alzheimer's disease,
but this hallmark represents a new target for Alzheimer's therapies.

Mice with Alzheimer's disease that underwent the therapy not only
exhibited a reduction in blood vessels and other Alzheimer's markers in
their brains, they also performed remarkably well in tests designed to
measure learning and memory.

"We are really very excited, because these findings suggest we can
repurpose approved anti-cancer drugs for use as treatments for Alzheimer's disease," said Professor Wilf Jefferies, the study's senior author
and principal investigator at the Centre for Blood Research, Vancouver
Prostate Centre and Michael Smith Laboratories. "It could shorten the
clinical development by years." Alzheimer's disease is estimated to
affect 50 million people worldwide. The condition is characterized by
cognitive decline, memory loss and dysfunctional changes in the brain.

Potential Alzheimer's treatments have shown promise in animal models
before, but failed in clinical trials. Typically, these strategies target
a protein called tau or a protein fragment known as beta-amyloid, but the
UBC researchers chose a different approach. They left the traditional
targets alone and instead focused on curbing angiogenesis: the growth
of new blood vessels.



==========================================================================
"The vast majority of clinical trials have either directly or indirectly targeted beta-amyloid or tau," said Prof. Jefferies. "Other than some controversial recent results, there's been a paucity of success in these clinical trials. So, a great deal of effort appears to have been directed toward the wrong targets for reversing Alzheimer's disease." Setting the
stage for the present study, Prof. Jefferies' earlier pioneering work
had shown that the proliferation of blood vessels compromises the blood-
brain barrier in patients with Alzheimer's disease. This barrier, made
largely of blood vessels, is believed to protect the brain from infection because foreign molecules cannot easily cross it.

Since cancerous tumours also rely on new blood vessel growth to survive
and thrive, the researchers reasoned that a proven anti-cancer drug
might halt the process in Alzheimer's.

"Axitinib, the anti-cancer drug we used, blocks a receptor in the
brain called a tyrosine kinase receptor, which is partly responsible
for spurring blood vessel formation," explained Dr. Chaahat Singh,
the paper's first author and a postdoctoral fellow working with
Prof. Jefferies. "It stops abnormal blood vessels from growing, which
then prevents many downstream effects." By using Axitinib for just
one month, the researchers dramatically reduced blood vessel growth,
restored the blood-brain barrier, and most significantly, helped mice
perform better on cognitive tests.



==========================================================================
In a typical test, a mouse is trained how to reach a reward through
a maze. A healthy mouse can find its way back to the reward, while an
animal with Alzheimer's disease symptoms cannot.

The treatment has only been applied to mice thus far. Clinical trials
will be needed to assess the effectiveness of this treatment in patients
with Alzheimer's disease, as well as consideration for the long-term
use of anti- cancer drugs in people living with Alzheimer's, who are
mostly elders.

Still, the researchers are optimistic. If Axitinib does work well in
humans, repurposing an already-approved drug could more rapidly advance
its use for Alzheimer's.

"Researchers including myself have been disappointed in observing
numerous clinical trials for Alzheimer's disease fail to reach their
clinical endpoints," said Prof. Jefferies. "The therapeutic approach
we discovered has an opportunity to revise the clinical treatment of Alzheimer's patients, which I think is absolutely needed at this point
for the field to advance." Prof. Jefferies and his collaborators have
shared their findings in EBioMedicine, published by The Lancet.

The Canadian Institutes of Health Research, the W. Garfield Weston
Foundation and the UBC Centre for Blood Research provided funding to
Prof. Jefferies for this research.

========================================================================== Story Source: Materials provided by University_of_British_Columbia. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Chaahat S.B. Singh, Kyung Bok Choi, Lonna Munro, Hong Yue Wang,
Cheryl G.

Pfeifer, Wilfred A. Jefferies. Reversing pathology in a
preclinical model of Alzheimer's disease by hacking cerebrovascular
neoangiogenesis with advanced cancer therapeutics. EBioMedicine,
2021; 71: 103503 DOI: 10.1016/j.ebiom.2021.103503 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124658.htm

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