Medical News A drug may prevent Alzheimer’s but there are no plans to find out
Large studies are needed before drugs can make it into pharmaciesPeoplepictures/Getty
By Debora MacKenzieAn 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-odd people 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 a full-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 the blood, 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 lower inflammation 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 drugs are badly needed.
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