Publish date: 13 January 2023

Breakthroughs in Alzheimer’s disease are exciting and invigorating dementia research, and we will need to be ready to deliver new treatments as they come through, say Professor Nick Fox and Dr Catherine Mummery.

For the first time in the world, a drug has been found to be able to reduce the rate of cognitive decline in Alzheimer’s disease.

In a trial including people with early-stage disease, lecanemab slowed cognitive decline by 27% over 18 months by lowering levels of the harmful protein amyloid in the brain. Amyloid has long been thought a major cause of Alzheimer’s disease, but its exact role in the disease has been unclear.

BRC supported clinicians Professor Nick Fox and Dr Catherine Mummery, who lead the UCL Dementia Research Centre, are at the forefront of dementia research and say the results of the study are game changing.

Prof Fox said: “I believe the results open a new era of disease modification for Alzheimer’s disease – an era that comes after more than 20 years of hard work on anti-amyloid treatments, by many people, with many disappointments along the way.

“The treatment produced a dramatic reduction in brain amyloid – to the point where many participants would be considered to have had such low levels of amyloid that they would no longer have been eligible for the trial.

There is still a lot we need to understand, says Prof Fox: “There are many unanswered questions. For example, do clinical benefits continue after 18 months? What happens if treatment is paused? And how early should it be started? Most of us would want our disease slowed when we still had a good quality of life and independent functioning.

“There are other challenges too. For instance, we will need to find new ways of delivering the therapy. The study involved intravenous infusions every 2 weeks which is a real burden on families. Sub-cutaneous treatments would be a step in the right direction.”

“However, for the millions of present and future patients globally, it is better to have these problems than no problems and no prospects.”

As in other disease areas, it is likely that a range of different treatments will be needed for patients with Alzheimer’s disease in future, and Dr Mummery said the lecanemab results will spur researchers on.

She said: “The results are tremendously exciting and they will reinvigorate the field. The lecanemab study proved the amyloid hypothesis in Alzheimer’s disease and the positive results will encourage more investment and focus on finding drugs to treat the disease, both against amyloid and against other targets, such as tau.”

Dr Mummery said: “We are conducting several early phase trials in therapies to try to change the course of disease, and we may now need to consider whether such trial drugs should be given in combination with lecanemab. One study will involve people at risk of a type of inherited Alzheimer’s disease and will use lecanemab in combination with an anti-tau treatment developed at UCL with the company Eisai.”

As research continues and hope grows for new treatments to come through, Prof Fox and Dr Mummery say that hospitals will need to be ready to be able to offer patients these new therapies.

Prof Fox said: “It is not enough to do the research. We need to be able to deliver the treatments once they are approved. As things stand at the moment, many hospitals would not have the capacity of infrastructure including PET or cerebrospinal fluid (CSF) capabilities to assess amyloid status in patients nor the MRI capacity for monitoring of safety. So assuming new treatments become available, hospitals will need the resources to be able to identify the patients who can benefit from these treatments and be able to deliver them.”

Dr Mummery said: “We will need to substantially develop our dementia treatment pathways in the UK so that we are able to diagnose Alzheimer’s early and accurately enough for drugs like lecanemab to have a chance to work, and to deliver new treatments safely.

“At UCLH we have the expertise and potential to develop a national flagship service to provide cutting edge treatments with support. The NHS and Trusts will need to consider how to resource these new treatments and the services that support them to change what is currently a palliative service for a terminal disease to an active management of a chronic disease. For our patients that would be a revolution.”