2020 ADDF-HARRINGTON SCHOLAR
RE-ENFORCING A BARRIER TO
PROTECT AGAINST ALZHEIMER’S FOCUS: Restoration of healthy Wnt signaling to prevent and/or allay Alzheimer’s disease. With more than 50 million people worldwide
“Wnt” are signaling proteins that are
“Thus, we hypothesize that inhibiting the
living with Alzheimer’s disease (AD), its
important in maintaining a healthy
increased Notum will help to restore Wnt
tragic results are impacting countless lives.
BBB, keeping nerve cells healthy, and
signaling, the result being a healthy BBB
A therapy that halts or slows the progress
promoting the clearance of toxic
in AD patients.”
of this disease is one of humankind’s most
proteins like tau and amyloid.
significant unmet needs.
Dr. Fish has indeed developed a potential Dr. Fish and his team have identified
drug that can inhibit Notum. He and his
The blood-brain barrier (BBB) controls
an enzyme at the BBB, called Notum,
collaborators have reason to believe this
what nutrients get into the brain from blood
which prevents Wnt signaling by
drug may even have the potential for use in
(e.g. glucose that provides energy). With
removing an essential palmitoleate
other conditions such as colorectal cancer.
AD, the BBB no longer functions properly,
group (fatty acid) from Wnt proteins.
With insights from his Harrington Discovery
and the brain receives insufficient glucose
“We have found that Notum is increased
Institute team, their drug is being rapidly
while allowing blood proteins to penetrate,
in mouse models of AD and in post-
progressed to testing in animal models
causing inflammation. Preventing this loss
mortem brain samples from AD
of AD and safety studies to determine its
of function could be a valuable therapeutic
patients,” Dr. Fish says.
suitability for treating AD patients.
approach for AD.
PAUL FISH, PhD Professor and Head of Chemistry Alzheimer’s Research UK UCL Drug Discovery Institute
“An invaluable asset in working with our Harrington team is being able to have critical and supportive peer reviews as we develop this drug.” 30
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HARRINGTON DISCOVERY INSTITUTE AT UNIVERSITY HOSPITALS
CLEVELAND | OHIO
