Beating Alzheimers one step at a time

Worryingly, 1 in 3 people in the UK over the age 65 will die with dementia, including with varients of it including Alzheimer 's disease. So the government and charitable funding bodies, have, over the last decade, identified this area as a major research strategic priority and pumped large amounts of cash being injected into research into the area.

So, why in that case, is diagnosis still so difficult? And why are the treatments currently on offer for Alzheimer's so inadequate? 

Eric -   I'm Eric Karran.  I'm Director of Research, Alzheimer's Research UK. 

Let's start with diagnosis.  So unfortunately, the brain is a kind of an isolated organ and it's behind bone, it's in the skull, compared to other organs like liver and heart, measuring its activity is actually quite challenging. 

Some of the clinical instruments that we currently use, the ways we have of assessing cognition and memory and learning are actually relatively crude still.  So, we're in a situation where it's quite difficult to measure subtle changes in cognitive function even though those changes themselves may herald the development of the disease. 

So, to make an analogy, if you have slightly high blood pressure, so rather than 120, it's 125 or 130, you can actually measure that very, very accurately and very, very easily.  You just put a cuff around your arm and you can measure that.  There's absolutely nothing comparable to that for measuring brain function at the moment.  So, we're in a situation where we still have relatively imprecise and crude tools with which to try and measure and diagnose brain function. 

I think the other issue is that different pathologies, different things going on in your brain can result in similar symptoms initially.  And so, there is significant overlap in some cases between the pathology of one disease such as frontal temporal lobe dementia and another disease such as Parkinson's disease.  And yet, the therapies for those are going to be radically different. 

So, we're in a situation where we don't have good instruments to measure brain function.  We don't have good diagnostic tests to know that person A has Alzheimer's disease versus another brain disease.  When you put that together, you end up with an incredibly challenging problem. 

I think the other issue is that these diseases, although they're very aggressive, the day to day or week to week change in cognition is actually relatively modest.  And so, in terms of trying to do a drug trial to work out if a medicine is working or not, you need to continue those trials for up to 1 ½ in 2 years at a minimum.  And so then you're in a position where you have people that you're not absolutely certain have the disease because of the issues of diagnosis.  You have to treat them for a very long time.  And then at the end of it, you have relatively imprecise tools to measure whether or not your drug is working.  And so, this I think explains to a large extent why we have struggled currently to find very effective therapies. 

I think that's changing.  We now have far better tools that can enable you to image the pathology of some of the diseases in living people without using invasive technology - so this is going in for brain scans.  And so, with these new instruments, firstly, we're going to be able to select people with better accuracy for particular drug trials.  So, we know that they've got the disease or the pathology that we hope to treat.  And also, we'll be able to measure the effects of the drugs objectively by looking at the spread or the inhibition of spread of pathology. 

And so, I'm very hopeful that we've had a decade of failure in this area, but with that failure comes learning as well.  What we understand that the pharmaceutical industries had a tough time trying to develop drugs that's usually expensive.  Unfortunately, some of them are withdrawing from this area to other areas where they can get a return on investment.

Hannah -   So, they're moving away from the brain because it is still such an enigma.  As you said, we don't have the tools for diagnosis in some disorders?

Eric -   Yes.  And so, if you look at where the market for drugs is growing, in other words, where countries are reimbursing the pharmaceutical industry with novel drugs, it's really in cancer, in arthritis, and in diabetes - those big three. 

They are unfortunately retreating from really tough areas such as Alzheimer's disease.  Not all of them.  Some are staying in the course, but many of them are having to close that down.  And you can understand that because they need to get a return on investment.  Unless they do that, they don't research anything.  So, that's a natural response. 

So, what we see as being important in terms of charities if you like, trying to fill that gap, that translational gap.  So previously, academics would do very novel research and the pharmaceutical industry would take a look at that research and say, "Of that research, what is it we think are going to provide promising targets for drugs ultimately?"  The pharmaceutical industry is not going to be doing so much of that anymore.  So, it's going to be up to academics and other groupings to be able to take up that challenge. And so, we're in a consortium where we'll be able to put money and to help those very early stage of discovery projects.  I think the other really exciting thing we're doing is, we'll be paying for drug discovery institute that will be housed within an academic institution.  So, this is really working very closely with academics to try and fashion their innovation and make it appropriate and right for patient benefit.

Hannah -   Do we know enough about the biology of Alzheimer's in order to start developing new drugs that can treat it?

Eric -   That's a good question.  I mean, you never know enough about a disease, but if I contrast what we know about Alzheimer's disease, where there's a pathology we understand, there are genetic risk factors we understand, if you contrast that Schizophrenia where it's incredibly mysterious what's going on there, I think we could always do with more knowledge, but I think we do have sufficient information to come up with new targets.

Hannah -   And so, how will these new drugs contrast with the current made of action of Alzheimer's drugs?

Eric -   The current drugs we have are what we call symptomatic.  So, they do something for some of the symptoms, but they're not particularly effective and their efficacy actually wears off pretty quickly with time.  The new drugs that we'll be able to look at are really either to try and prevent, or slow down, the spread of two of the major pathological proteins in the brain.  One is called A-beta, the other is called tau. 

I think in the future, there's a lot of research going into tau pathology and there are some very promising drugs coming forward which seem to be able to prevent the spread of that pathology through the brain.  Certainly, in animal systems, they do that.  The spread of that pathology in human disease correlates very well with the loss of brain cells, and also, with the onset of dementia.  So, I think that is going to be a really promising area in the future to look at.

Hannah -   Thanks to Eric Karran at Alzheimer's Research UK.