Finding the right drug for Alzheimer's

17 June 2014

Interview with

Chris Dobson, University of Cambridge

In the drive to find a drug that prevents Alzheimer's disease, scientists are using fruitpills flies as a model organism to screen various compounds that could one day lead to a cure. Hannah Critchlow spoke to Cambridge neuroscientist Chris Dobson to find out more.

Chris D. -  I've been described as many things.  I mean, our view is that many of the diseases in the past or all of the diseases I think in the past really, until you understand the real mechanism, it's almost impossible to develop effective drugs.  I think this has been one of the problems so far in trying to treat Alzheimer's disease.  So, what we're trying to do in fact is to take the Abeta peptide that Jody mentioned and understand exactly the mechanism by which it begins to clump together the steps that it goes through, how it forms species that are toxic, why they're toxic, and how it eventually forms to plaques.  And we found a lot out about that and we've done that in the test tube.  And so, what we want to do now and what we're beginning to do now is to say, "Does the same sort of thing happen in living systems?"  We've taken very simple organisms.  You're going to ask me about the fruit fly which is one of the ones...

Hannah -  I am about to.  I've heard rumours that you work with the common garden fruit fly that maybe hover above people's bananas as they get a little bit mouldy.

Chris D. -  We do.  I hope these ones don't hover around people's bananas, but what we're really trying to do there is actually to generate what we sometimes call test tubes with wings that we can put via transgenic means by genetic engineering the same peptide - the Abeta peptide - into the brains of fruit flies.  And then we can choose lines of flies which have much the same sort of symptoms as you see in Alzheimer's disease.  They form plaques, they have difficulty moving around.  We haven't checked very carefully what they can remember, but we know that they actually don't live so long and so forth.  That gives us a system where we can look at thousands or millions of flies to get statistics on the way that molecules interact with the Abeta peptide.  And so, what we're able to do is to take molecules we found in the test tube and see what effect they have in these model organisms.

Hannah -  And so, you are able to really screen new compounds or compounds that are in existence at the moment.

Chris D. -  Absolutely.

Hannah -  And find out if they can revert this misfolding of this protein that's toxic to nerve cells and stop it from causing Alzheimer's.

Chris D. -  Absolutely and I think there are really two aims that we would have.  One is to reduce the risk of it, the chance of this happening which of course would be a bit like a sort of statin for heart disease, it just makes it less likely you'll get it.  The other is actually, to try to do therapeutic, a real cure.  Well at least, to find a molecule that will stop this process occuring so the disease doesn't progress.  So, we're able to test these ideas out in these simple systems.

Hannah -  I mean, the drugs that are currently used for those people that have Alzheimer's, what do they do?  Do they not affect all these protein misfolding and try and revert that?

Chris D. -  Well actually, what they don't do is actually slow down at all the progression of disease.  There's no evidence that any current drugs actually have an effect on the progression of disease I'm afraid.  What drugs do do is how to alleviate some of the symptoms.  And so, that's really all we can do for patients at the moment.  But I hope of course that we can find drugs that will actually supress the processes that give rise to a disease.

Hannah -  And that's why it's so imperative that you continue your work looking at the chemistry, this basic biology in trying to develop new compounds.

Chris D. -  Absolutely and I think we heard from some young people.  I think they're the people who need to be aware of what's going on because it takes a long time to develop drugs.  The amount we spend on research in Alzheimer's disease is minute compared to the amount we spend on cancer and heart disease even though the cost of society and economy are much greater in Alzheimer's disease.

Hannah -  Jody.

Jody -  Yeah, just following on from that point really, it costs the UK economy 23 billion pounds a year.  It's just huge and with the numbers going through the roof, that's only going to get a lot worse.  You know, it's set to hit a million and then start doubling every sort of 25 years, and I mean, with the game in particular, we're trying to get young people interested in an area that they probably don't think is going to affect them.  But the young people of today are going to become the carers of tomorrow.

Hannah -  I suppose previously there was quite a lot of stigma around Alzheimer's disease as there was with cancer.  So patients that had cancer 50 years ago, they didn't want to mention the C word.

Chris D. -  I think it's absolutely right.  50 years ago, if someone was diagnosed with cancer, the question was, "Did you tell them?"  And the answer is, you didn't normally tell them because it was almost nothing you can do.  I think the developments in the 1970s, particularly in 1971 National Cancer Act in the US opened up the whole field and people started talking about it, therapists started appearing, a lot more money was put into it, a lot more people are engaged in it, and that's absolutely what we need to do now.  So, these methods that Jody is talking about, to get people aware of the disease, and aware that we can do something.  I'm very optimistic.  I think we can have dramatic effects on the onset of disease and prevention of disease, but it's going to take a long time.  It's going to take a lot of effort just as cancer did.

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