15 June 2019 | New Scientist | 7Analysis Drug development
AN ARTHRITIS drug seems to
significantly cut the risk of developing
Alzheimer’s disease – but there are
no plans to find out if it really works.
Last week, The Washington Post
reported that pharmaceutical firm
Pfizer has data showing that an
arthritis treatment it owns called
Enbrel may also lower the risk of
getting Alzheimer’s by 64 per cent.
But, according to critics, Pfizer
has elected not to develop the
drug for this condition because
the patent on it will soon expire,
meaning the company won’t
profit from pursuing it further.
Pfizer, however, denies the patent
was a factor. There are ways to
extend patents if something appears
profitable – and, with an estimated
37 million people with Alzheimer’s
worldwide, a drug for this disorder
surely would be. The company
told The Post that it just wasn’t
convinced by the data.
Enbrel, also known as etanercept,
is currently used to treat rheumatoid
arthritis by helping to rein in the
body’s inflammatory response.
It contains a protein that binds
to TNF-alpha, a master-signal
released by cells to trigger
inflammation when they detect
something foreign, like bacteria.
Inflammation is useful for
destroying pathogens, but it
can also harm the body, and it is
involved in a number of diseases
associated with ageing. Like
rheumatoid arthritis, Alzheimer’s
is known to involve TNF-alpha.
Pfizer’s findings are reported to
have come from mining insurance
company data sets that include
millions of people’s diseases,
treatments and outcomes.
Of about 400 people with
rheumatoid arthritis, those
on Enbrel seemed to be less
likely to go on to develop Alzheimer’s
than those on other treatments.
Pfizer never published this
analysis, but the link is no secret.
In 2016, Richard Chou, now at
the State University of New York
at Buffalo, and his colleagues
published their own analysis of
insurance records. Of 300-oddpeople with rheumatoid arthritis,
those on Enbrel were about a third
as likely to get Alzheimer’s as those
on other treatments. Small trials
in Taiwan and the UK have also
found that Enbrel may improve
Alzheimer’s symptoms.
“We have been saying for a
decade that mopping up TNF with
etanercept will have a beneficial
effect in Alzheimer’s,” says Bryce
Vissel at the University of Technology
Sydney. He is frustrated that afull-blown trial still hasn’t been done.
The difficulty of trialling
treatments for Alzheimer’s disease
is the real problem here. A drug
needs to be tested on thousands
of people before it can be licensed
for a disease, and Alzheimer’s trials
are especially expensive because
they take many years. According
to Chou, we don’t know enough yet
to justify launching such a trial for
Enbrel. “The epidemiological data
are a good start, but not sufficient
to initiate a clinical trial,” he says.
Besides being lengthy and
costly, there is a third reason
pharmaceutical firms are currently
reluctant to conduct Alzheimer’s
drug trials. To date, all of these have
been based on the hypothesis that
the disease is caused by an excess
of a molecule called amyloid.
But all these trials have failed.
Having lost vast sums pursuing
one hypothesis, companies are
reluctant to chase another: that
Alzheimer’s is brain damage caused
by chronic inflammation.
Enbrel may well prevent this. Pfizer
told The Post it was partly deterred
from investigating further because
the drug, when given normally in theblood, is blocked by the blood-brain
barrier and cannot enter the brain.
But this isn’t a reason to think that
Enbrel won’t work for Alzheimer’s,
says Keenan Walker of Johns Hopkins
University in Maryland. TNF-alpha
outside the brain starts or worsens
inflammation inside the organ,
by triggering inflammatory signals
that do cross the barrier.
So drugs like Enbrel that lower
TNF-alpha inflammation outside
the brain could also result in lowerinflammation inside it. “I think a
proper trial for anti-TNF-alpha drugs
such as etanercept should be
considered,” says Walker.
But who will conduct it? Clive
Holmes at the University of
Southampton, who ran the UK trial
of Enbrel in Alzheimer’s patients, is
pursuing further small-scale trials.
But “a positive independent study
will still not lead to a treatment
unless you have the backing of
pharma”, he says.
However, all major firms have
now closed their Alzheimer’s units.
Pfizer hasn’t entirely given up on the
condition, though. The firm is a major
investor in Cortexyme, a company
investigating the relationship
between Alzheimer’s, inflammation
and the bacteria that cause gum
disease. Nevertheless, no major
company capable of organising
large, long studies looks likely to
risk setting up another expensive
Alzheimer’s trial any time soon.
If companies can’t develop such
vital drugs, some observers have
suggested other ways should be
found, such as government funding.
With Alzheimer’s expected
to affect some 56 million people
by 2030, there is no doubt the
PEOdrugs are badly needed. ❚PL
EP
ICTURES
/GETTYLarge studies are needed
before drugs can make it
into pharmacies
Why a possible Alzheimer’s drug may never be trialled
An arthritis drug might prevent Alzheimer’s, but the firm that
owns it isn’t keen to develop it. Debora MacKenzie reports
There are
no effective
treatments
available for
Alzheimer’s yetGE
TTY“ We have been saying for
a decade that this kind
of drug will be beneficial
for Alzheimer’s disease”