Alzheimer’s drugs offer little benefit, major review finds – and the reasons go deeper than the science

A new review of the evidence has concluded that the leading class of Alzheimer’s drugs “probably result in little to no difference” in a range of measures, including reducing dementia severity. This finding was quickly used to further justify the NHS’s decision two years ago not to fund these drugs.

These findings are disappointing, not just for researchers and drug companies, but also for the tens of millions of people and their families suffering from the effects of a devastating disease.

Medical research is often reported through success stories, but Alzheimer’s disease has remained stubbornly resistant to the development of life-changing breakthroughs. This has not gone unnoticed. A couple of years ago, investigative journalists uncovered significant fraud in important studies underpinning some of the science behind the leading Alzheimer’s drugs.

While this fraud is not solely responsible for the lack of progress in Alzheimer’s research, it does reveal how vested interests can distort science and how commercial interests can sometimes override indications that a specific approach may not actually be working. It also reveals how social, political and economic factors can distort and hold back entire fields of research.

A century of science and still no answers

The German psychiatrist Alois Alzheimer first identified the disease that bears his name in 1906. Over the subsequent years, it was found to be characterised by abnormal protein deposits in the brain called amyloid “plaques” and similarly misfolded protein tau tangles.

As these misfolded proteins are not found in healthy brains, it was assumed that they were the cause of the disease. But subsequent studies showed that the amounts of these protein deposits did not correlate well with disease severity, unlike similar diseases, where misfolded protein deposits occurring in other parts of the body led directly to organ failure.

This complex relationship between the pathological changes in the brains of people with Alzheimer’s and the psychological progression of the disease has split the research field for many years.

At one point, those proposing that amyloid deposits (or at least the molecular processes leading to them) were the main cause of the disease were even referred to as “Baptists”, while those holding tau as responsible were called the “Tauists”. Although these have been the main two theories as to the cause of the disease, there have been numerous others, such as linking the disease to the abnormal behaviour of neurotransmitters, inflammation, presence of pollutants, age-related changes, DNA damage, viruses and even sleep disturbance.

In situations like this, when there are many competing theories, researchers who start working on one theory can start to become entrenched. This is an unfortunate byproduct of competitive funding models, where research money tends to flow to the researchers who are most successful at arguing that their approach is the most promising and therefore worthy of receiving more research money. This is an interesting example of how science is not always an entirely objective endeavour.

This pressure on researchers to publish papers and attract funding is probably a contributing factor to the significant fraud linked specifically to some working on the amyloid hypothesis for Alzheimer’s. In one case, a researcher in the US was forced to resign from his university following the retraction of a much-cited paper, and the discovery that over 20 other papers may have similarly questionable data.

In a separate case, an academic faced fraud charges, while a pharmaceutical company they worked with came under investigation for allegedly misleading investors. Both of these cases were in connection with a different approach to treating Alzheimer’s, namely, targeting a protein called filamin A.

Indeed, controversies within Alzheimer’s research have become so frequent that they have inspired an entire book dedicated to examining the issue.

Matthew Schrag, a neuroscientist who played a key role in exposing elements of fraud in Alzheimer’s research, said: “You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can’t cheat to cure a disease. Biology doesn’t care.”

While scientific breakthroughs undoubtedly underpin much of modern life, the example of Alzheimer’s research serves as a reminder that the path from defining a problem to discovering a solution is rarely straightforward.

It would be nice to think that the main incentive for most researchers might be solving a problem or curing a disease, but the actual situation is far more complex. Research relies on funding, and researchers get jobs based on reputation, often in the form of publications. Because of this, the wrong behaviour can become incentivised.

The complexity of Alzheimer’s disease and the lack of obvious answers or cures make this field particularly susceptible to distortion by the social factors that can influence science.

As researchers and pharmaceutical companies compete for funding and investment, the science starts to get lost behind the games that are played. The end result is not only financial loss and lack of progress, but in the case of this devastating disease, millions of people also end up suffering through a lack of effective treatments.

Simon Kolstoe, Associate Professor of Bioethics, University of Portsmouth

This article is republished from The Conversation under a Creative Commons license. Read the original article.