2023 has been a momentous year in Alzheimer’s research with the milestone of a second medicine being approved by the FDA in America.
Aduhelm and Leqembi are two medicines that target the disease-related molecule known as amyloid beta. It has long been a goal of the dementia research community to develop drugs that lower levels of this protein, although some have argued that chasing this single target has slowed progress in other areas.
Whatever the target for new medicines, dementia research has been frustrated by the lack of effective treatments. This is evident from a study indicating that there is a 0.4% success rate for Alzheimer’s disease clinical trials.
So, for these two medicines to have navigated the complex route to approval is a remarkable success. It also indicates that fundamental research pays dividends but takes time to bring the benefits to those living with dementia. We will have to wait and see if the UK regulators approve Leqembi as only the FDA has approved both Aduhelm and Leqembi to date.
The new medicines are monoclonal antibodies, which we have heard lots about through the COVID-19 pandemic. In a wealth of studies, data demonstrated a reduction of amyloid beta following administration of these medicines.
The critical step was to demonstrate if this reduction would bring about changes in the individuals living with dementia. In one study, Leqembi was shown to slow down the course of disease progression by 27%, following 18 months of treatment. There are, however, restrictions on its use, so it is not available for all those living with dementia. The study indicated that those with a specific genetic fingerprint (at least one copy of the risk gene ApoE4) are at greater risk of adverse side effects so need to be aware of these elevated risks if they wish to take Leqembi. This is the genetic fingerprint that the Australian actor, Chris Hemsworth recently revealed he had.
As lab-based dementia researchers, we welcome these successes in clinical trials but they do not conclude our efforts to find new medicines and ways of managing the disease for people living with dementia.
My own research has been looking at how brain cells change in response to disease, inflammation as a global response to disease, and how we can detect this and suppress any damaging inflammatory responses.
This research involves looking at the immune cells of the brain, called microglia. Seen as ‘first responders’, we believe changes in these cells occur well before an individual visits their GP to discuss changes in their behaviour or memory loss.
We can grow these cells in the lab and monitor their activity over time and when we expose them to various chemicals that we know are disease related.
One study is looking at the ability of microglia to digest waste material of the brain. This process called autophagy, which is derived from the Greek meaning of ‘eating of self’, provides essential housekeeping services for the brain to maintain optimal communication between cells.
Research indicates that this process becomes disrupted in Alzheimer’s disease and so new molecules that target this process hold promise as therapies further down the line.
This research is fascinating and reveals complexities about the brain that we still do not fully understand. There is a real drive in the global dementia research community to follow up these successes with new molecules to be tested.
To get a sense of the scale of international dementia research, at the start of 2023 there were 187 trials assessing 141 drugs for the treatment of Alzheimer’s disease and it is predicted that some 57,000 participants will be required to evaluate these.
So, for 2023 we should celebrate these successes as transforming the landscape of clinical Alzheimer’s disease and look forward to better and new medicines for the future. This will hopefully bring the benefits of Alzheimer’s treatments to a wider range of individuals that are living with the disease.