‘This looks like the real deal’: are we inching closer to a treatment for Alzheimer’s? - The Guardian

No one expects it to stop cognitive decline, but even slowing it would be a breakthrough.

At the end of November, thousands of researchers from around the world will descend on San Francisco for the annual Clinical Trials on Alzheimer’s Disease meeting.

The conference is a mainstay of the dementia research calendar, the place where the latest progress – and all too often, setbacks – in the quest for Alzheimer’s treatments are made public for the first time.

After more than a century of research into Alzheimer’s, scientists expect to hear details of the first treatment that can unambiguously alter the course of the disease.

It gave top-line results from a major clinical trial of an antibody treatment, lecanemab, given to nearly 2,000 people with early Alzheimer’s disease.

The therapy slowed cognitive decline, the statement said, raising hopes that a drug might finally apply the brakes to Alzheimer’s and provide “a clinically meaningful impact on cognition and function”.

But others counter that any effect on Alzheimer’s deserves celebration: it proves the disease can be beaten, or at least slowed down.

“Dementia is a global economic disaster as people are institutionalised while their disease progresses at huge cost to society and healthcare systems,” says Prof Giovanna Mallucci, former centre director of the UK Dementia Research Institute at the University of Cambridge, now principal investigator at Altos Labs.

“When you have that first breakthrough, it’s like the hole in the dyke that leads to a bigger hole,” says Prof Bart De Strooper, director of the UK Dementia Research Institute at University College London.

“This is not a cure by any stretch of the imagination, but if it does slow cognitive decline, it means that for the first time we are modifying the disease,” says Dr Richard Oakley, head of research at the Alzheimer’s Society.

The cognitive decline in Alzheimer’s arises from the relentless destruction of neurons, the cells that ferry information around the brain.

The effect goes far beyond normal age-related brain shrinkage: on death, a patient’s brain can weigh 140g less than before the disease took hold – a reduction of more than 10%.

In some families blighted by early onset Alzheimer’s, scientists have found mutations that cause abnormal clumps, or plaques, of a brain protein called amyloid beta to build up between neurons.

In most patients, the decline is likely to be driven by a messy mix of processes, which fuel one another.

None slowed cognitive decline; some even made it worse.

The problem is compounded by the insidious early phase of the disease, which destroys neurons without people noticing.

While press-released data from the lecanemab trial suggests the drug slowed cognitive decline, the effect was small.

It’s not large enough to be clinically important,” says Prof Victor Henderson, director of the Alzheimer’s Disease Research Center at Stanford University.

One idea gaining ground in Alzheimer’s research is that drugs will need to remove amyloid fast to have any hope of showing a clinical benefit.

“What really needs to be trumpeted from this trial [assuming the results hold up] is that you can change the rate of decline of the disease.

If Alzheimer’s patients can benefit from amyloid-clearing treatments, they will need an early diagnosis and evidence of amyloid in the brain.

Antibodies may help some Alzheimer’s or pre-Alzheimer’s patients, but to have a major effect on the disease, a combination of drugs that hit different biological processes is needed.

A new clinical trial at the University of California, San Diego, is about to test whether a BDNF-boosting gene therapy can help patients with early Alzheimer’s