Alzheimer's - hope, hype and the here and now

More great news about a drug breakthrough that could bring relief to people with Alzheimer’s set me thinking about the balance between hope and hype in the search for cures for degenerative conditions.

Donanemab is the second drug in a year which has been shown to slow the progress of Alzheimers. Its maker Eli Lilley reported that a late-stage trial found that it slowed the worsening of symptoms by 40% over 18 months compared with people given a placebo. Like Lecanemab, which sparked headlines last year as the first drug to slow Alzheimer’s, it works by attacking the sticky amyloid protein in the brain thought by many (though not all) researchers to cause the degenerative disease.

There have been excited headlines about this latest advance, with many zeroing in on a quote from the associate director of research at the Alzheimer’s Society:

“This could be the beginning of the end of Alzheimer’s disease,” said Dr Richard Oakley, the kind of authoritative source that any journalist would be happy to quote. What is encouraging for anyone with Parkinson’s is that both these drugs aim to change what is happening in the brain - the same disease modification path that scientists looking for a cure for our condition are pursuing.

But not so fast - we may need to keep the champagne on ice for a while. For one thing, Donanemab has some serious side-effects with two participants in the Phase 3 trial dying after a swelling of the brain. For another, the drug is only really likely to be useful for people whose Alzheimer’s is at an early stage.

It’s also clear that the debate over the causes of Alzheimer’s and other neurodegenerative diseases is far from over. Just a few days before the Donanemab announcement the venerable New Scientist magazine ran. a leader column with the headline “Brain boost - a “grand unifying theory” of brain disease deserves our cautious respect.”

Now, at first I assumed it must be about the idea that amyloid was responsible for Alzheimer’s, Parkinson’s and other brain diseases but no, the article. was about another theory - that a deficiency of mitochondria, described as cellular power stations supplying the brain with energy, was the cause. Indeed, the leader column referred to. the “now infamous amyloid theory”, suggesting it had sent researchers down the wrong path.

I’ve been speaking to one leading researcher in this field who thinks the hype around these drugs has gone too far. Roxana Carare, professor of clinical neuroatomy at Southampton University, has spent 25 years trying to work out what is happening inside the brains of people who develop Alzheimer’s, Parkinson’s and other neurological diseases. She explains that it’s the clogging up of the brain’s waste disposal system which is the focus of much of the research she and others are undertaking - but that there is still far too little known about how that works, which is why we have to be sceptical about new “wonder drugs.”

She is scathing about the claims made for the new drugs without a clear understanding of their effects on the brain.  “What I find absolutely unbelievable. is that with all the billions of dollars that have been thrown at these trials, nobody's collecting the brains of patients who die.” She says that only by analysing brains of drug trial participants after death can there be clarity about whether Lecanemab and Docanemab have made a difference.

Professor Carare says she understands the need, as she puts it, not to “put the brakes on public hope.” But she warns that, outside the United States, people with Alzheimer’s and their families shouldn’t be investing that hope in Docanemab: “It will never be approved in Europe because the side effects are so intense, the cost is gigantic - it’s 10s of thousands of dollars for an infusion and you need one every month.”

Where Roxana Carare does see hope is in treatment that can alleviate the symptoms of Alzheimer’s here and now. In particular, she’s a fan of Media v Dementia, the project launched by the former TV producer Michael Blakstad. This aims to stimulate the brains of people with dementia by offering them a personalised menu of video clips, photos and music which stir memories, and is a modern updating of something called reminiscence therapy.

The professor says there is science behind the idea in that it can help the brain’s waste disposal system work better: “The way in which we eliminate waste is along tiny channels embedded in the walls of the blood vessels,” she explains: “if we keep the vessel active and pumping, we're also keeping those channels open.” Personalised media, she says, can provide an exercise regime for the brain to keep it running smoothly.

To be fair, the Alzheimer’s Society has recognised the need for this kind of innovation while the expensive hunt for wonder drugs continues:

“While we await these new drugs, we need to improve the lives of people living with dementia,” the charity said in a letter to the Guardian last week. It says it is hoping to stimulate the growth of “new assistive technologies using recent advances such as artificial intelligence” with its £4m Longitude Prize, which it is funding with Innovate UK.

Compared with the huge budgets poured into trialling new drugs such as Docanemab £4 million is small change. But there is a good chance that, in the short term at least, that money will have a much bigger impact on the lives of people living with dementia.