Drug trial raises fresh hopes in hunt for Alzheimer's treatment

A long-awaited drug treatment which can halt Alzheimer’s disease may be on the horizon after promising results from an early stage clinical trial.

Experts are taking care not to build up false hopes about the antibody drug, aducanumab, which clears away sticky protein fragments in the brain linked to Alzheimer’s.

But according to one leading charity, the first disease-modifying therapy for the devastating brain condition may now be within sight.

Dr David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “These results provide tantalising evidence that a new class of drug to treat the disease may be on the horizon.

“The findings suggest that aducanumab may slow memory and thinking decline in people with early Alzheimer’s and, although the analysis is only exploratory in this early trial, it paints a positive picture for ongoing trials with the drug.”

The last Alzheimer’s drug licensed in the UK became available more than a decade ago. Current treatments can reduce symptoms to some extent but doctors have nothing that can halt or slow progression of the disease.

An estimated 850,000 people in the UK suffer from some form of dementia, most having Alzheimer’s. By 2025 their numbers are expected to swell to more than a million.

Alzheimer’s is linked to the build up of sticky clumps of beta-amyloid peptide – pieces of protein – in the brain. Extensive deposits of the material can be seen in the brains of dead victims.

Beta-amyloid toxicity is thought to be a primary cause of the neural dysfunction and degeneration which underlies the disease.

Scientists have long known that removing beta-amyloid could lead to a glittering prize – halting or at least slowing Alzheimer’s progression. But until now all attempts to target the peptide with a drug have met with failure.

Aducanumab is a monoclonal antibody – an immune system agent copied and produced in a laboratory which selectively targets beta-amyloid.

Tests on mice genetically engineered to develop a disease similar to Alzheimer’s showed that the drug could enter the brain and reduce levels of beta-amyloid in a dose-dependent fashion.

Scientists also conducted an early Phase I trial to evaluate the safety and tolerability of monthly aducanumab injections in patients displaying early symptoms of Alzheimer’s disease.

A total of 165 patients received monthly infusions of either aducanumab or a placebo “dummy drug” for one year.

After 54 weeks of treatment, scans showed that levels of beta-amyloid had been significantly reduced in the brains of patients given the antibody. Higher doses were associated with greater reduction, the researchers reported in the journal Nature.

At the higher doses, removal of beta-amyloid was also associated with slower mental decline. However, the preliminary study was not designed to assess aducanumab’s clinical effectiveness, which will now have to be tested in larger trials.

Recruiting of patients for bigger trials, including participants from the UK, has already started.

Reynolds said some side effects seen in the Phase I study were “concerning” and would have to be addressed. These included headaches and mostly related to abnormalities revealed by the scans.

The Alzheimer’s Society said the “most compelling” evidence from the trial was the fact that more beta-amyloid was cleared when patients took higher doses of the drug.

Dr James Pickett, head of research at the charity, said: “No existing treatments for Alzheimer’s directly interfere with the disease process, and so a drug that actually slows the progress of the disease by clearing amyloid would be a significant step.

“While there were hints that it might have an effect on the symptoms of the disease, we need to see the results from further, larger research trials to understand whether this is the case. These larger trials are now under way, including in the UK, and due to finish in 2020.”

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