Bexarotene – a drug approved in the US for the treatment of
lymphoma – has shown potential in halting the first stages of Alzheimer’s
disease, according to a research. Researchers are now looking at developing a
treatment that can be taken as a preventative measure long before symptoms
develop. However, they do not wish to propose bexarotene as a cure for
Alzheimer's disease, but they suggest it could diminish the risk of developing
the disease by boosting the body's natural defenses against faulty proteins in
the brain.
German neuropathologist Alois Alzheimer
described 2 hallmarks of Alzheimer’s disease – tau tangles developing
inside neurons, caused by a build-up of tau protein, and amyloid plaques,
developing between brain cells, caused by an accumulation of sticky protein
fragments called amyloid beta. Scientists believe these plaques and tangles
weaken communication between nerve cells, which in turn harms the processes
that helps brain cells to survive.
Researchers found bexarotene after searching a library of 10,000
small molecules they assembled by looking for compounds that interact with
amyloid beta. [Read more Exposure
to environmental toxin may increase risk of Alzheimer's]
After observing the effects of these faulty proteins in a
lab model of Alzheimer's, scientists have discovered that an already approved
anti-cancer drug could delay the onset of the neurodegenerative disease. [Read
more Eating
sweet food forms memory of the meal – findings could encourage novel treatment
for obesity]
Michele Vendruscolo, senior autho and a professor in the
department of chemistry at the University of Cambridge said:
"By understanding how these natural defenses work, we
might be able to support them by designing drugs that behave in similar
ways."
For the study, Professor Vendruscolo and her colleagues –
researchers from Cambridge, the University of Groningen in the Netherlands and
Lund University in Sweden – worked with nematode worms that were engineered to
develop Alzheimer's disease. At various stages of the disease, the worms were
given the cancer drug, bexarotene, which has seen mixed results in treating
Alzheimer’s in the past.
The researchers found that the drug disrupted the first
steps in the process of amyloid plaque formation called primary nucleation. Primary
nucleation occurs when naturally occurring proteins 'misfold' themselves and
clump together with other proteins to form thin filament-like structures called
amyloid fibrils, and smaller protein clusters called oligomers. However, the
drug did nothing to combat symptoms that had already appeared, such as the
appearance of dense clusters of beta-amyloid molecules. [Read more একা খাওয়া আপনার স্বাস্থ্যের জন্য মারাত্মক ক্ষতিকর হতে পারে]
"We
showed that these worms that were doomed to develop Alzheimer’s disease could
be rescued," said Prof. Vendruscolo.Although research to prevent oligomer formation in Alzheimer’s has been going on for over 20 years, researchers have not made headway. Prof. Vendruscolo and colleagues believe this is because it is not known how the disease starts at the molecular level. [Read more Can Turmeric Prevent Alzheimer’s?]
Key finding of the study is that the researchers demonstrated exactly what happens at each stage of Alzheimer's disease, and what might be the result of a particular stage being interrupted or switched off.
This is not the first time bexarotene has been used in
Alzheimer’s research. Earlier studies of bexarotene have suggested that the
drug could actually reverse Alzheimer’s symptoms by clearing amyloid beta in
the brain. The results however, were disputed. What this study has shown, is
that the drug is ineffective in clearing protein clumps, but could play a role
in stopping them from forming in the first place.
"Even if you have an effective molecule, if you target the wrong step in the process, you can actually make things worse by causing toxic protein assemblies to build up elsewhere."
Rosa Sancho, head of research at Alzheimer's Research UK, who was not involved in the study said:
"A recent clinical trial of bexarotene in people with
Alzheimer’s was not successful, but this new work in worms suggests the drug
may need to be given very early in the disease. We will now need to see whether
this new preventative approach could halt the earliest biological events in
Alzheimer’s and keep damage at bay in further animal and human studies."
The study was published in Science Advances.
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