Despite promising results in an earlier trial, people taking the experimental drug intepirdine in the Phase III MINDSET trial did not see any substantial benefits in memory and thinking compared to those who took a placebo. These disappointing results feel like yet another setback, but Dr Clare Walton our Research Communications Manager explains why we should still be optimistic.
A drug to manage the symptoms of dementia
Intepirdine was being tested as an add-on to existing Alzheimer’s medications. It wasn’t expected to slow down the brain damage caused by Alzheimer’s, but based on earlier studies, researchers were hopeful that it would go further than the existing drugs to help people cope with the symptoms of dementia.
Given that we haven’t seen a drug approved for any form of dementia since 2002, new approaches to treat the symptoms and to slow the disease are both urgently needed.
Over 1000 people with mild to moderate Alzheimer’s disease took part in the trial. They took either the experimental drug or a placebo every day for 6 months, on top of a stable daily dose of donepezil, the most common treatment for Alzheimer’s.
At the end of the study, there were no significant differences in memory and thinking abilities between those who took the drug and those who took the placebo. There were also no improvements in how well people were able to complete their daily activities such as dressing, cooking and using public transport.
The conclusion – that intepirdine does not work as a new drug for people with Alzheimer’s.
Broadening the focus of drug discovery
It’s true that drug discovery for Alzheimer’s disease has been riddled with negative results, but this latest failure isn’t a reason to lose hope. Up until now, most Alzheimer’s drug research has focused on a very narrow range of targets. Drugs in development have either focused on the build-up of amyloid plaques, or have tried to change the imbalance of chemicals called neurotransmitters in the brain. This is what intepirdine does.
Although we know both of these mechanisms are important in Alzheimer’s, we also know of several other pathways that go wrong and contribute to disease progression. Alzheimer’s Society has recently committed £50m as a founding funder of the UK Dementia Research Institute, which will fund over 400 scientists to investigate the underlying causes of all forms of dementia. By exploring a much wider range of disease mechanisms, their research aims to unlock the doors to many alternative treatment approaches.
Researchers within the UK Dementia Research Institute, and indeed across our £30m research portfolio, are looking into a number of exciting leads. These include: the critical role that cells and chemicals of the immune system play in dementia; the way in which connections between brain cells are disrupted early in the disease; what changes in the complex relationship between blood vessels and brain cells as dementia takes hold; and more exploratory work such as the role of sleep and gut bacteria in predisposing people to dementia.
Working across these diverse research areas and casting our net more widely should dramatically increase our chances of finding new drugs that really work.
Dr Doug Brown, our Director of Research and Development, said: ‘The UK Dementia Research Institute is a ground-breaking initiative that could not have arrived at a better time. As the number of people living with dementia in the UK is set to reach 1 million by 2021, the stakes are too high to fail.’
Time is of the essence
Of course for people living with dementia now, time is still the most important issue. With another drug failure comes the disappointment that it will be a few years before we see the next promising drug trial deliver its results. While we wait, we need to look at ways to shortcut the drug development process – which is the focus of our Drug Discovery programme. It tests whether drugs already in use for other health conditions such as diabetes, rheumatoid arthritis or high blood pressure, can work for people with dementia too, potentially reducing development time in half.
We’re also investing heavily into care research that looks at non-pharmacological ways to help people with dementia manage their symptoms and to be supported to live in their communities as well as possible for as long as possible.