Alzheimer’s research is gaining ground. Recently, two new drugs - lecanemab and donanemab - have proven to significantly slow the spread of the disease in clinical trials. Both drugs work by removing amyloid, a toxic protein in the brain linked with Alzheimer’s.
These drugs are disease-modifying therapies, meaning that they tackle the root causes of Alzheimer’s itself - as opposed to current treatments approved for use in the UK, which only manage disease symptoms. The success of these drugs in trials has brought hope, and this has been hailed as a turning point in dementia research.
Despite this breakthrough, much progress still needs to be made. Although lecanemab and donanemab slow the disease, there is debate over whether these effects can significantly impact the life of somebody with Alzheimer’s, especially when weighed up against the drugs’ potential side effects. Additionally, the drugs work less effectively in some people than others. These limitations likely arise as amyloid is only one part of the picture: there are many other factors in the brain and body that contribute to Alzheimer’s.
Targeting these other factors alongside amyloid may lead to a more comprehensive and effective therapy programme. In this article, we will discuss some of these promising targets.
Tau: another hallmark disease protein
Amyloid isn’t the only toxic protein linked with Alzheimer’s: another protein called tau is also responsible. Normally, tau helps to maintain the structure of neurons in the brain. However, in Alzheimer’s, an abnormal form of tau, which disrupts neuron structure, accumulates instead. Compared to amyloid, the tau protein correlates more strongly with neurodegeneration.
This means that targeting tau can lead to extremely impactful treatments for Alzheimer’s - and it’s a major target being looked at by researchers. Of all Alzheimer’s drugs that are currently undergoing clinical trials, tau-targeting drugs make up a significant portion. These drugs include antibodies designed to attack the tau protein itself, drugs that stop tau proteins from clustering together, drugs that stop tau from being produced in the brain, and more.
As of now, two tau-targeting drugs are in Phase 3, the final stage of clinical trials. These drugs are E2814, an anti-tau antibody; and LMTM, which prevents tau proteins from clustering and dissolves existing clusters. Eight more drugs targeting tau are currently in Phase 2 clinical trials.
Research led by UK DRI scientist Dr Will McEwan has found a way to optimise future antibody therapies targeting tau. Dr McEwan discovered that a certain immune mechanism in the brain cells deteriorates tau proteins, while avoiding negative inflammatory side effects. Future treatments harnessing this mechanism could be much safer while still effective.