Disease-modifying treatments for Alzheimer’s disease

It is unprecedented times for people working in neurodegeneration and Alzheimer’s disease (AD) with the advent of disease-modifying therapies, according to Prof Iracema Leroi, Professor of Geriatric Psychiatry at Trinity College Dublin, and the Global Brain Health Institute. She is also Consultant Geriatric Psychiatrist at St James’s Hospital, Dublin.

Prof Leroi delivered a presentation on the new class of treatments for AD at the College of Psychiatrists of Ireland Winter Conference 2023. She also discussed the outcomes of a working group which was convened to consider the implications of, and health system readiness for, disease-modifying treatments (DMTs) for the disease in the Irish context.

Speaking to the Medical Independent (MI), Prof Leroi said that there were significant challenges in Ireland to ensure these treatments were accessible and appropriate people received them.

“There is a lot of public education that has to occur to ensure that these things are happening, and that people’s expectations are managed, and they get the opportunity to receive treatment. But we are still a long way away, and a lot of work has to be done. I think Ireland has a tremendous potential to do this in the best possible way because we are a small community, we know each other, and we can work together.”

Prof Leroi told MI: “The support we have from the HRB [Health Research Board] in moving the research agenda forward for this population is absolutely critical.”

In her presentation, she told delegates that there was no licensed treatment to delay or slow the progression of the neurodegeneration that characterised AD until recently. “However, over the past decade, evidence supporting the potential for dementia prevention through risk reduction has increased, alongside a growing pipeline of medications with the potential for disease modification, targeting the very earliest stages of AD, mild cognitive impairment, and the mild stages of dementia.”

She explained that of the current ongoing trials of nearly 130 agents for AD worldwide, about 80 per cent were classified as DMT, as opposed to symptomatic therapies for cognitive enhancement or management of neuropsychiatric symptoms. “The current potential DMTs for AD include human monoclonal antibody-based agents targeting beta amyloid, two of which have recently received regulatory approval from the FDA in the US. While promising for the treatment of AD in Ireland, the complexity of drug eligibility, administration, cost, and safety of the DMTs necessitate adopting new models of treatment and care pathways to AD.”

Prof Leroi is Co-Lead of Dementia Trials Ireland (DTI), which has recently been established. DTI is a research network, funded by the HRB, to increase the capability and capacity for conducting trials in dementia and people at risk of dementia in Ireland. It is an interdisciplinary group, formed to increase the involvement of people living with dementia in clinical trials.

“It is very important that people with dementia are counted and get the opportunity to become involved in research.”

Prof Leroi also highlighted that access to treatment was essential. “It’s all very well coming up with cutting-edge DMTs, but if you cannot implement these because you do not have the right ecosystem or environment, you’re essentially wasting your time.” In addition, improvements in the diagnostic landscape were also required.

“If you wait for clinical symptoms to appear, the horse has bolted. So, you need to start early in the pre-clinical stage. That is the holy grail in all neurodegenerative diseases. Because you have to be able catch it. But if you cannot detect the disease, you cannot treat it.”