Alzheimer’s disease could be treated with a commonly used
anti-inflammatory drug, which has been proven to reverse brain inflammation and
memory loss, a new study has revealed.
Researchers from the University of Manchester found the
common anti-inflammatory drug 'mefenamic acid' completely reversed memory loss
and brain inflammation in mice.
The drug, mefenamic acid is a common Non-Steroidal
Anti-Inflammatory Drug (NSAID) that many people have used in their lives
already and is most commonly used to ease period pain.
The findings of the study have been published in the journal
Natural Communications by author of the study Dr David Brough and his
colleagues: Dr Catherine Lawrence, PhD student Mike Daniels, and Dr Jack
Rivers-Auty.
Dr David Brough commented: “There is experimental evidence
now to strongly suggest that inflammation in the brain makes Alzheimer’s
disease worse.
“Our research shows for the first time that mefenamic acid,
a simple Non-Steroidal Anti-Inflammatory Drug can target an important
inflammatory pathway called the NLRP3 inflammasome, which damages brain cells.”
“Until now, no drug has been available to target this
pathway, so we are very excited by this result.
“However, much more work needs to be done until we can say
with certainty that it will tackle the disease in humans as mouse models don’t
always faithfully replicate the human disease.
“Because this drug is already available and the toxicity and
pharmacokinetics of the drug is known, the time for it to reach patients
should, in theory, be shorter than if we were developing completely new drugs.
“We are now preparing applications to perform early phase II
trials to determine a proof-of-concept that the molecules have an effect on
neuroinflammation in humans.”
More than 500,000 people in the UK have Alzheimer's disease
with symptoms predicted to worsen over time. The disease affects all aspects of
their lives, including their ability to think, remember and make decisions on a
daily basis.
Completely reversing memory loss
Researchers in the study set out to establish whether
existing anti-inflammatory drugs could be used to block inflammatory activity
of the NLRP3 inflammasome complex.
The team found that a group of anti-inflammatory drugs
called fenamates blocked the effects of NLPR3 whereas others, like ibuprofen,
did not.
Researchers studied transgenic mice to see if they developed
the symptoms of Alzheimer's disease. One group of 10 mice was treated with
mefenamic acid, and 10 mice were treated in the same way with a placebo.
The mice were treated at a time when they had developed
memory problems and the drug was administered for one month to test the
effects.
The study revealed that memory loss was completely reversed
back to the same levels seen in mice without the disease.
Head of research at Alzheimer’s Research UK, Dr Rosa Sancho
said: “There is increasing evidence of a key role for the immune system in
Alzheimer’s, making it an attractive target for the development of new
treatments for the disease. This research in mice suggests that an existing
anti-inflammatory drug could have an effect on an important Alzheimer’s disease
process. This finding is promising and will need following up to explore in
more detail whether this class of drug could hold potential as a treatment for
Alzheimer’s.
“Studying the effect of drugs for Alzheimer’s in mice is an
important step that can provide valuable insights. However, carefully
controlled clinical trials are vital for establishing the safety and efficacy
of any treatment in people.
“Research like this is crucial as there are currently no
treatments that can alter the progression of Alzheimer’s in the brain or
protect nerve cells from damage in the disease. Drugs that act against the
immune system have real potential to limit damage in Alzheimer’s and
Alzheimer’s Research UK is investing heavily in this approach through our drug
discovery initiatives. We desperately need to see greater investment in
research if we are to find new ways to help the tens of thousands of people who
develop Alzheimer’s in this country every year.”
The research was funded by the Medical Research Council and
the Alzheimer’s Society, and could pave the way for human trials in the future.
'Promising results'
This is the first time a drug has been shown to target this
particular inflammatory pathway, highlighting its importance in the disease
model. However, Dr Brough warned that more research was required to identify
its impact on humans and the long-term implications of its use.
Director of research and development at Alzheimer’s Society,
Dr Doug Brown added: “Testing drugs already in use for other conditions is a
priority for Alzheimer's Society - it could allow us to short cut the 15 years
or so needed to develop a new dementia drug from scratch.
“These promising lab results identify a class of existing
drugs that have the potential to treat Alzheimer's disease by blocking a
particular part of the immune response.
“These drugs are not without side effects and should not be
taken for Alzheimer's disease at this stage - studies in people are needed
first.”
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