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