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  • I'm very pleased to be here today

  • to talk to you all about how we might repair

  • the damaged brain,

  • and I'm particularly excited by this field,

  • because as a neurologist myself,

  • I believe that this offers one of the great ways

  • that we might be able to offer hope

  • for patients who today live with devastating

  • and yet untreatable diseases of the brain.

  • So here's the problem.

  • You can see here the picture of somebody's brain

  • with Alzheimer's disease

  • next to a healthy brain,

  • and what's obvious is, in the Alzheimer's brain,

  • ringed red, there's obvious damage -- atrophy, scarring.

  • And I could show you equivalent pictures

  • from other disease: multiple sclerosis,

  • motor neuron disease, Parkinson's disease,

  • even Huntington's disease,

  • and they would all tell a similar story.

  • And collectively these brain disorders represent

  • one of the major public health threats of our time.

  • And the numbers here are really rather staggering.

  • At any one time, there are 35 million people today

  • living with one of these brain diseases,

  • and the annual cost globally

  • is 700 billion dollars.

  • I mean, just think about that.

  • That's greater than one percent

  • of the global GDP.

  • And it gets worse,

  • because all these numbers are rising

  • because these are by and large

  • age-related diseases, and we're living longer.

  • So the question we really need to ask ourselves is,

  • why, given the devastating impact of these diseases

  • to the individual,

  • never mind the scale of the societal problem,

  • why are there no effective treatments?

  • Now in order to consider this,

  • I first need to give you a crash course

  • in how the brain works.

  • So in other words, I need to tell you

  • everything I learned at medical school.

  • (Laughter)

  • But believe me, this isn't going to take very long.

  • Okay? (Laughter)

  • So the brain is terribly simple:

  • it's made up of four cells,

  • and two of them are shown here.

  • There's the nerve cell,

  • and then there's the myelinating cell,

  • or the insulating cell.

  • It's called oligodendrocyte.

  • And when these four cells work together

  • in health and harmony,

  • they create an extraordinary symphony of electrical activity,

  • and it is this electrical activity

  • that underpins our ability to think, to emote,

  • to remember, to learn, move, feel and so on.

  • But equally, each of these individual four cells

  • alone or together, can go rogue or die,

  • and when that happens, you get damage.

  • You get damaged wiring.

  • You get disrupted connections.

  • And that's evident here with the slower conduction.

  • But ultimately, this damage will manifest

  • as disease, clearly.

  • And if the starting dying nerve cell

  • is a motor nerve, for example,

  • you'll get motor neuron disease.

  • So I'd like to give you a real-life illustration

  • of what happens with motor neuron disease.

  • So this is a patient of mine called John.

  • John I saw just last week in the clinic.

  • And I've asked John to tell us something about what were his problems

  • that led to the initial diagnosis

  • of motor neuron disease.

  • John: I was diagnosed in October in 2011,

  • and the main problem was a breathing problem,

  • difficulty breathing.

  • Siddharthan Chandran: I don't know if you caught all of that, but what John was telling us

  • was that difficulty with breathing

  • led eventually to the diagnosis

  • of motor neuron disease.

  • So John's now 18 months further down in that journey,

  • and I've now asked him to tell us something about

  • his current predicament.

  • John: What I've got now is the breathing's gotten worse.

  • I've got weakness in my hands, my arms and my legs.

  • So basically I'm in a wheelchair most of the time.

  • SC: John's just told us he's in a wheelchair

  • most of the time.

  • So what these two clips show

  • is not just the devastating consequence of the disease,

  • but they also tell us something about

  • the shocking pace of the disease,

  • because in just 18 months,

  • a fit adult man has been rendered

  • wheelchair- and respirator-dependent.

  • And let's face it, John could be anybody's father,

  • brother or friend.

  • So that's what happens when the motor nerve dies.

  • But what happens when that myelin cell dies?

  • You get multiple sclerosis.

  • So the scan on your left

  • is an illustration of the brain,

  • and it's a map of the connections of the brain,

  • and superimposed upon which

  • are areas of damage.

  • We call them lesions of demyelination.

  • But they're damage, and they're white.

  • So I know what you're thinking here.

  • You're thinking, "My God, this bloke came up

  • and said he's going to talk about hope,

  • and all he's done is give a really rather bleak

  • and depressing tale."

  • I've told you these diseases are terrible.

  • They're devastating, numbers are rising,

  • the costs are ridiculous, and worst of all,

  • we have no treatment. Where's the hope?

  • Well, you know what? I think there is hope.

  • And there's hope in this next section,

  • of this brain section of somebody else with M.S.,

  • because what it illustrates

  • is, amazingly, the brain can repair itself.

  • It just doesn't do it well enough.

  • And so again, there are two things I want to show you.

  • First of all is the damage of this patient with M.S.

  • And again, it's another one of these white masses.

  • But crucially, the area that's ringed red

  • highlights an area that is pale blue.

  • But that area that is pale blue was once white.

  • So it was damaged. It's now repaired.

  • Just to be clear: It's not because of doctors.

  • It's in spite of doctors, not because of doctors.

  • This is spontaneous repair.

  • It's amazing and it's occurred

  • because there are stem cells in the brain, even,

  • which can enable new myelin, new insulation,

  • to be laid down over the damaged nerves.

  • And this observation is important for two reasons.

  • The first is it challenges one of the orthodoxies

  • that we learnt at medical school,

  • or at least I did, admittedly last century,

  • which is that the brain doesn't repair itself,

  • unlike, say, the bone or the liver.

  • But actually it does, but it just doesn't do it well enough.

  • And the second thing it does,

  • and it gives us a very clear direction of travel for new therapies --

  • I mean, you don't need to be a rocket scientist

  • to know what to do here.

  • You simply need to find ways of promoting

  • the endogenous, spontaneous repair that occurs anyway.

  • So the question is, why, if we've known that

  • for some time, as we have,

  • why do we not have those treatments?

  • And that in part reflects the complexity

  • of drug development.

  • Now, drug development you might think of

  • as a rather expensive but risky bet,

  • and the odds of this bet are roughly this:

  • they're 10,000 to one against,

  • because you need to screen about 10,000 compounds

  • to find that one potential winner.

  • And then you need to spend 15 years

  • and spend over a billion dollars,

  • and even then, you may not have a winner.

  • So the question for us is,

  • can you change the rules of the game

  • and can you shorten the odds?

  • And in order to do that, you have to think,

  • where is the bottleneck in this drug discovery?

  • And one of the bottlenecks is early in drug discovery.

  • All that screening occurs in animal models.

  • But we know that the proper study of mankind is man,

  • to borrow from Alexander Pope.