Page 50 - 04_May-2025

In the brain, amyloid acts like a wrecking ball, disrupting
communication between neurons, and further
knocking out memories while impairing cognition.
He felt motivated to learn more, shifting his focus so entirely
that studying Alzheimer’s disease became a full-time occupation.
He was in good company. When Jhamandas started his
research, a cottage industry was forming in the medical
community. For a long time, researchers have known that those
with diabetes are much more likely to get dementia. Common
to both conditions is a rogue protein called amyloid that can
negatively affect a variety of vital functions in the body. In
the brain, amyloid acts like a wrecking ball, disrupting com-
munication between neurons, and further knocking out
memories while impairing cognition.
Many other scientists with magnitudes more resources had
also tried but failed to stop amyloid. A trial vaccine in the early
2000s helped the body develop antibodies against it but some-
times also caused major inflammation, causing the drug to be
shelved. Next came genetically engineered or chemically
synthesized antibodies. While these improved cognition for
those with early signs of Alzheimer’s, occasional, irreversible
side effects such as brain swellings made these treatments too
risky as well. Researchers also tried to stop amyloid from
forming in the first place.
Over the years, several drugs have been released that can
temporarily improve cognitive function by boosting levels of
the acetylcholine, a chemical that helps transmit signals
between nerve cells, and is often depleted in Alzheimer’s patients.
These therapies alleviate symptoms, but don’t stop them. And
there are diminishing returns. The further the disease progresses,
says Jhamandas, the less effective those drugs become.
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Today, his work tests the hypothesis that drugs developed
for blocking amylin — which influences blood glucose levels for
diabetes patients — might also protect the brain from amyloid.
Jhamandas is optimistic. The first real breakthrough, he says,
happened recently; several therapies can in fact remove that
rogue protein from the body.
Jhamandas saw positive results quickly. His
team started by testing two drugs already effective in treating
diabetes, applying them first to mouse brain cells in a Petri
dish, then to mouse brain slices, and eventually to live mice.
The drugs, it turned out, were protecting the brain cells from
death or destruction caused by amyloid. And the work began
to attract attention.
Though not from everyone. Jhamandas met with eight
pharmaceutical companies to potentially partner with, but they
were wary of the nature of the drugs being peptides, or chains
of amino acids, the building blocks of proteins. These can be
barred by the blood-brain barrier, a kind of filter built into
blood vessels that protects the brain. Those peptides can
also be degraded by enzymes in the blood, and, in general, are
extremely expensive to make. The other challenge was that
the end product was likely in a needle — a potential marketing
nightmare.
Then, eight years ago, Jhamandas was giving a lecture attended
by Dr. Lorne Tyrrell, founding director of the Li Ka Shing
Institute of Virology at the University of Alberta. The institute