Plaque busting drug shows early promise in preventin...

"A revolutionary drug that could stop people from ever developing Alzheimer's disease has been unveiled," the Daily Mail reports.

The drug, aducanumab, encourages the immune system to attack the abnormal plaques of protein linked to Alzheimer's disease. However, the reporting on this story should be treated with caution because the study it's based on was not big enough to reliably show the drug can affect mental decline.

The study of 165 people with early stage Alzheimer's disease tested a new immunotherapy drug, aducanumab, to see if it could get rid of lumps of protein, called amyloid beta plaques, from the brain. These plaques, which are usually seen in the brains of people with Alzheimer's disease, are thought by many doctors to be the cause of the mental decline seen in the disease. However, this theory is not yet proven. It could still be the case that the plaques are actually a byproduct of another underlying cause.

The study authors wanted to see whether the drug removed the plaques, and was safe to use. The study was not designed to show whether it affected mental decline, although the researchers did look at that outcome too.

Some experts have called the results of the study "tantalising," as they give good reason to continue with larger studies of this drug. However, we won't know if it works to halt or reverse Alzheimer's disease until the results of bigger studies, which are now underway, are in.

Where did the story come from?

The study was carried out by researchers from Biogen (the company which makes aducanumab) and Butler Hospital in the US, and the University of Zurich and Neurimmune in Switzerland. It was funded by Biogen. It's normal for a drug manufacturer to fund research into its own drug. The study was published in the peer-reviewed journal Nature.

The Daily Mail said aducanumab was "revolutionary" and predicted "the end of Alzheimer's," with healthy older people being given the drug as a preventive measure in the same way statins are used for heart disease prevention. Such claims are far too premature.

The Guardian was more measured, saying the trial showed "tantalising signs" that aducanumab could benefit patients with early-stage Alzheimer's. The Guardian's clear and detailed coverage stated from the start that the study was only preliminary and does not prove that the drug works to improve mental functioning.

By contrast, The Daily Telegraph said: "scientists proved they can clear the sticky plaques from the brain which cause dementia and halt mental decline". The study proved nothing of the kind. The link between the plaques and cognitive decline, while plausible, is unproven.

What kind of research was this?

This was a randomised controlled trial of 165 people with early or mild Alzheimer's disease. It is a phase 1b trial designed to investigate the safety, effects and side effects of the drug on the brain. These studies are typically done in the early stage of drug research, to decide whether it's worth continuing to full clinical studies that can tell us whether the drug actually works.

What did the research involve?

Researchers recruited 165 Americans with a clinical diagnosis of early-stage Alzheimer's disease and randomised them into groups. One group had placebo injections while the others had monthly injections of aducanumab, at different doses, for one year. They had positron emission tomography (PET) scans of their brains and took tests of cognitive function at the start of the study, after 24 weeks and 52 weeks.

The study was designed to be big enough to see what happened to the brains of the people with Alzheimer's disease. However, the series of tests of cognitive function tend to show less clear-cut results and so need more people to take part, to be sure the results are accurate, and not down to chance.

There were 40 people in the placebo group and 31 or 32 in the four other groups which were given different doses. As well as looking at brain scans and cognitive outcomes, the researchers monitored the patients for adverse effects which might have been caused by the drug.

What were the basic results?

Brain scans showed that patients who took the drug had cleared large areas of beta amyloid plaque by the end of the study. Those who took the highest dose had levels of amyloid plaque almost down to normal levels. The amounts of amyloid plaque declined over the course of the study.

The cognitive tests showed that, in all but the highest dose group, everyone who finished the study had a decline in mental function over the year. People who took the highest dose showed little change in mental function over the year. The study suggests that people who took intermediate doses had a slower decline in mental function than those taking placebo, but the difference was too small to be sure that was not just down to chance.

Not everyone finished the study. Of the 165 people who started it, 40 stopped treatment, 20 of them due to adverse effects. The most worrying adverse effect was an increase in swelling of the blood vessels in the brain. This happened to 41% of the people taking the highest dose. Although no-one needed hospital treatment, the condition could increase the risk of small bleeds in the brain. The next most common adverse effect was headache.

How did the researchers interpret the results?

The researchers say their results show that their drug works to reduce amyloid plaques in the brain, and that the cognitive test results support the theory that removing plaques benefits mental function.

"The clinical study results provide robust support to the biological hypothesis that treatment with aducanumab reduces brain amyloid beta plaques and, more importantly, to the clinical hypothesis that amyloid beta plaque reduction confers clinical benefit," they write.

They conclude that the results "justify further development of aducanumab for the treatment of AD".

Conclusion

Drug research into treatments for Alzheimer's disease has been going on for many decades and results so far have been disappointing. That's one reason why many people are cautious about news of a new Alzheimer's "breakthrough". Many people living with Alzheimer's disease, and their friends and loved ones, have had their hopes raised too many times.

So it's important to be clear about what this study does and does not tell us:

The study doesn't show whether the drug works to halt mental decline.
The results don't show whether the drug can reverse symptoms of Alzheimer's disease. The best we can say from these results is that it may slow or halt the progress of mental decline in people with early Alzheimer's disease – but that the results are not strong enough to be sure.
The study doesn't tell us for sure whether amyloid beta plaques cause Alzheimer's disease symptoms.
The study does show that the drug may reduce the amount of amyloid beta plaques in the brains of people with early Alzheimer's disease.

The main limitation of the study is its size, and the high numbers of people who dropped out. Small studies tend to have less reliable results and we don't know whether the results might have been different, had those who dropped out carried on with the study.

The excitement among researchers is understandable – the study shows clear signs that the drug has an effect on beta amyloid plaques. But we'll have to wait for the results of full clinical trials, involving tens of thousands of people, before we know whether this is really the "game changing" treatment that people have been waiting for.