A surprising
discovery has been made in the treatment of Alzheimer's disease. An
anti-inflammatory drug used to treat menstrual pain completely reversed memory
symptoms in mice with Alzheimer's.
The drug, called mefenamic acid, is a so-called
non-steroidal anti-inflammatory drug, or NSAID, used to relieve menstrual
cramps. In experiments with mice specially bred to have Alzheimer's symptoms,
the rodents predictably developed memory problems over time.
Ten of the Alzheimer's mice were treated for one month
with mefenamic acid that was contained in tiny pumps implanted under their
skin. Ten other mice with memory difficulties were injected with pumps of a
placebo, or inactive substance.
The rodents were placed in maze to train them to get
around the obstacles.
In a Skype interview, Mike Daniels, who participated in
the research at the University of Manchester in Britain, said, "We tried
to train the mice once they had Alzheimer's disease. The Alzheimer's mice are
untrainable. They cannot learn that maze."
But the results in the treated mice were stunning.
"What was just amazing is that this drug seemed to
render the mice completely normal,” Daniels said. “It's something we haven't
really seen before, but there needs to be a lot more work done to really
confirm whether this is real.”
Targeting
inflammation
The findings were published in the journal Nature
Communications. The research was led by David Brough of the University of
Manchester. Mike Daniels said brain-imaging shows a lot of harmful inflammation
in the brains of Alzheimer's patients. Researchers believe mefenamic acid
targets an inflammatory pathway called NLRP3, reducing inflammation. At the
same time, scientist found that no other NSAIDS — including ibuprofen, which is
commonly taken for pain — reduced the brain inflammation.
Whether it would work in patients at all stages of
Alzheimer's — from people with mild cognitive impairment to those who are
severely affected — is difficult to say, according to the study authors.
"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," Brough said.
Co-author Jack Rivers-Auty said, "Maybe, if this was
translated into the clinic, we would definitely want to put it into people at
the early stages of the disease to try to slow the progress or stop the
progress of the disease," Rivers-Auty said.
"Rather than taking the ambitious aim of taking
someone who fully has Alzheimer's disease, has all the symptoms — incredible
memory loss, incredible cognitive impairment — and trying to reverse those
symptoms. That might be very difficult," he added.
Mefenamic acid already has been approved by regulators
so, after further testing, it could reach the market relatively quickly as a
treatment for Alzheimer's disease.
Why Mice?
Many studies make use of lab mice to test drugs before
human trials can get started, but it's never a sure bet that researchers will
be able to reproduce the same results from animal trials in testing with human
beings.
One of the reasons mice are used in so much research is
because they share a lot of genetic material with humans – up to 97.5 percent
by some estimates. They're also easy to handle and have short lifespans, which
makes it easier to study successive generations more quickly.
But despite the similarity between genomes, more recent
research suggests mice and humans differ in the way they regulate genes – and
that might be one of the reasons why successful treatments on mice don't always
work in people.
What Next?
As stated, trials on animals are not the same as human
trials and may yield different results. However, if the proposed human trials
prove to be promising, it won’t be long before the treatment reaches patients.
“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,”
Brough said.
Dr. Doug Brown, Director of Research and Development at
Alzheimer's Society, backs this by saying, “Testing drugs already in use for
other conditions is a priority for Alzheimer’s Society — it could allow us to
shortcut the fifteen years or so needed to develop a new dementia drug from
scratch.”
There is also a note for caution attached with the
research.
“These promising lab results identify a class of existing
drugs that have potential to treat Alzheimer’s disease by blocking a particular
part of the immune response. However, 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,” Brown said in the statement.
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