The Pros and Cons of Donanemab: A New Breakthrough in Alzheimer’s Research?

‘Yes! We have no bananas’ is the attitude of a fruit seller who brings what he does not have with an optimistic sound. On the internet I read the amusing history behind the expression that led to a famous song by Frank Silver and Irving Cohn in 1923. We are a century later and the phenomenon still occurs daily. Especially in medicine where tubers are still sold like lemons. When it comes to cancer, we are used to seeing a revolutionary breakthrough every time. Which is never there. This is not to say that nothing has been achieved. I’m not going to pretend to oversee the field of cancer medicine, but as a semi-layman, I also know that oncology today is a lot more subtle and circumspect about cancer than we did in the 1960s. But there has never been one major discovery that brought about a profound revolution. It was always millimeter work that led to considerable profit over the years.

Today we have dementia

What is difficult to assess is the role of what is called ‘public opinion’. Cancer was once the most feared public disease (‘doctor, it’s not a K, is it?’) that could only be discussed with trepidation. That’s over now, not because there’s less cancer, but because we now have dementia as the new anxiety-giver. And just as with cancer, there is often a ‘breakthrough’ in dementia.

In 2008, the Janssen-Cilag company introduced galantamine (Reminyl). Their motto was: ‘Take action before your mother mixes everything up’. I’m afraid it’s still prescribed. But it doesn’t do anything. I know that ‘nothing’ can be nuanced in all sorts of ways to ‘something you hear!’ but in the end it’s just as good as nothing.

A new comet

A new comet has appeared in the firmament: donanemab. It involves an antibody that attaches to amyloid, which is then cleared by the immune system. Alzheimer’s, the most common form of dementia, is caused by the accumulation of proteins between brain cells, the amyloid plaques. But wait: there’s something else going on with Alzheimer’s. Something also happens inside the brain cells, that is where it originates number-tangles (tangles of a protein called tau). We don’t know why those tangles and those plaques form.

We do know that vascular damage is often the cause of Alzheimer’s. Smoking, high blood pressure, diabetes, little exercise, these are the factors that negatively affect the quality of our blood vessels. Only until now no one has been able to demonstrate a connection between those plaques and tangles and these striking risk factors for Alzheimer’s. It is now well known that the damage in the brain is about twenty years in the making before the brain owner actually starts to lose in terms of mental functioning.

Whether amyloid overload causes dementia is questionable. If you find a rabbit in almost every car accident, that does not mean that the rabbit causes all car accidents. If the number of accidents decreases dramatically after removing all rabbits, then it’s time to find out exactly what those rabbits are up to.

So it is with amyloid. Donanemab (think of it as a mnemonic of kebab for customs) eventually removes amyloid, but there is certainly no question of a dramatic effect. For 76 weeks, 1,200 people with early onset Alzheimer’s were given donanemab via an intravenous drip every month. Scoring lists showed that the cognitive decline in the treated group was 35 percent less. These scoring lists offer a view of many aspects of functioning. Nearly half of the patients did not deteriorate at all for a year. Now no one knows very well what the usual deterioration is, so this is difficult to weigh. Alzheimer’s is often very fickle.

How much does this donane kebab cost? It is estimated several tens of thousands of euros per patient per year. Yes, someone is going to walk in. Couldn’t this amyloid clearing be a mini-achievement on the road to a cure for Alzheimer’s after all? I hope so, but the role of amyloid is uncomfortably doubtful. The only thing we may know now is that with customs mab it may take you a little longer to lose yourself in dementia.