Science Interviews

Interview

Fri, 16th Sep 2016

Why Alzheimer's drugs keep failing

Professor Simon Lovestone and Jennifer Lawson, University of Oxford

Listen Now    Download as mp3 from the show Will We Beat Alzheimer's Disease?

If we know tau tangles and amyloid plaques are the cause of Alzheimerís, why An assortment of drugscanít we just blitz them? Kat Arney put this to Simon Lovestone...

Simon - We now know how the amyloid that forms the plaque gets formed and there have been drugs designed to prevent that formation or, indeed, to clear that plaque once itís already formed. Theyíve gone through clinical trials; so far none of those clinical trials have worked. I think thereís a different reason why they havenít worked; I donít think itís just because the drugs are no good.

Kat - What is that reason? You canít give me that teaser and not tell me.

Simon - The trials are done too late. So one other thing, and this is surprising; we didnít know this until a few years ago but those plaques and tangles start to form ten, perhaps twenty years before there are any clinical symptoms. So this is not doctors not picking up dementia, thatís another problem; this is there is no dementia, there are no clinical symptoms and thatís probably because the brain is such an amazing organ. Itís plastic, itís able to cope with a certain amount of damage without causing symptoms. So thereís this long period, up to twenty years, where the disease is happening but there are not symptoms. Now the trials, theyíre done in people with dementia. I think, and I think the majority of the world thinks, those trials are done way too late. Itís too much to ask these particular drugs to have a substantive effect after twenty years of disease.

Kat - What we need to do then, is spot the disease earlier. But thatís not easy, especially since people donít have symptoms until very late on. However, Simon and his colleague Jennifer Lawson have won a huge Medical Research Council grant for a clinical trial that they hope will change that by finding biomarkers. Much like a blood test can reveal a high levels of antibodies, and therefore whether you have an infection, Simon and Jennifer hope to find some similar marker for Alzheimerís. Hereís Jennifer...

Jennifer - Weíre going to take about two hundred and fifty volunteers and ask them to take part in the study. These are people who might have a range of health profiles; some people might appear be more at risk of getting Alzheimerís disease than others and what we want to do is track the really early changes that happen in the human body before we see memory changes.

Kat - So these are people who donít have Alzheimerís and also you donít know that theyíre going to get Alzheimer's?

Jennifer - Thatís right. We donít know if theyíre going to get Alzheimerís. At the moment, we know there are various genetic factors that make somebody more at risk of getting Alzheimerís. But we know thatís not the whole picture and we urgently need to find other ways of tracking Alzheimerís well before people end up with memory problems so that we can target treatments at people, at that stage, and we can run clinical trials in that population as well. And thatís the stage at which we think itís most likely to make a difference to peopleís lives.

Kat - So with this study youíve got these two hundred and fifty people. What are you doing with them - how are you studying them to try and find these markers that may show that they are or arenít going to develop the disease?

Jennifer - We are going to use every test we can think of that might show us something valuable in this population. So we will do a whole host of tests; theyíll be about fifty tests on people over a twelve month period, so itís quite intensive. Weíre going to do MRI scans, thereíll be MEG scans, and PET scans, so three different types of brain imaging in the same population in the same volunteers.

Kat - Thatís a lot of brain scanning!

Jennifer - Thatís a lot of brain scanning - yes. And thereíll be blood tests, thereíll be cognitive tests alongside which tests peopleís memory, reasoning, and thinking skills. Weíll also do eye tests looking at the retina at the back of the eye; we think we might be able to detect some changes in the morphology of the blood vessels at the back of the eye there and possibly pick up some early degeneration well before you see any other changes. Weíre also looking at wearable technologies, so thereís lots of things to look at peopleís gait and movement. Really subtle things that you wouldnít pick up yourself with your fitbit; these are like more highly specialised pieces of equipment that are being used to detect really subtle changes, so that needs to be analysed by some proper science in a lab.

Kat - So say you come up with this profile; this sort of set of measurements that you can say okay, this person is getting worse or this person is getting better. What happens next?

Jennifer - Once we have a set of biomarkers that weíre quite confident will show us how someone is progressing with Alzheimerís disease, we can then start to trial Alzheimerís drugs in a more effective way. In recent years, ninety-nine per cent of clinical trials in treatments of Alzheimer's disease have failed. It might be that many of those drugs actually would be effective if only we could target people at the right time. So we might be able to retest some of those compounds that previously havenít worked or we might be able to generate new compounds at the areas we have picked up from this trial.

Kat - If we can pick up the disease much earlier on, then, could we also screen for it? I put this to Simon Lovestone as my grandmother had Alzheimerís and I was keen to know if I, or my parents could be testedÖ

Simon - The short answer to that is no. And Iím not sure that weíd want something either. Right now we donít have any drugs for dementia and really you donít really want to screen until youíve got something you can do if you find out youíre screened positive.  We are though trying to work on tests or biomarkers for dementia and the reason why we arenít though is not to screen populations but to help in the diagnostic process.

So when an older person comes to the GP and says theyíve got memory problems right now, itís almost impossible to tell whether that is just the memory problems that happens as people get to be elderly, or whether itís the start of the dementia process. So we really like tests to help that clinical practice but, even more than that, we need biomarkers or tests to help do clinical trials earlier in the disease process more effectively. Thatís what we really want to test for, not for screening.

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