Ecstasy et Parkinson- Ecstasy & Agony:
Découverte
-Radio-Canada Émission du 20 janvier 2002
Sommaire- abstract
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Tim
Lawrence a 34 ans; il est cascadeur. Depuis cinq ans, il a appris une
terrible nouvelle qui a bouleversé sa vie. Tim est atteint de la maladie de
Parkinson, un mal qui paralyse lentement son corps sans affecter son cerveau.
Il y a trois ans, Tim a trouvé un moyen inusité de soulager ses symptômes.
Mais il y a un problème : il a recours a une drogue de la rue, illégale et
dangereuse. Cette découverte fortuite pourrait remettre en question un
concept scientifique reconnu depuis trente ans et mener à un tout nouveau
traitement de la maladie de Parkinson. |
Tim Lawrence was a film stuntman, appearing in
Braveheart and London's Burning. But at the age of 34 Tim was diagnosed with
Parkinson's Disease - an illness usually associated with the elderly. BBC2
9.00pm Thursday 15th February 2001 |
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Cependant voici le texte anglais de cette emission tirée
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Ecstasy & Agony:
Copie complete -transcript
BBC2 9.00pm Thursday 15th February
2001
Tim
Lawrence was a film stuntman, appearing in Braveheart and London's Burning. But
at the age of 34 Tim was diagnosed with Parkinson's Disease - an illness
usually associated with the elderly.
Tim now spends much of his time either frozen and unable to move, or twitching
uncontrollably. There is, however one thing that relieves Tim's symptoms, one
that challenges the medical community. The trouble is it involves an illegal
and dangerous street drug - Ecstasy.
Horizon follows the story of how Tim's inadvertent discovery is brought to the
attention of medical scientists, and is now being studied in the hope of
producing a new treatment for Parkinson's Disease (PD).
Parkinson's Disease is caused by the loss of a brain chemical called dopamine,
which is vital for movement. The result in Tim is the slow freezing up of his
body. But, like many people who contract the illness early in life, Tim suffers
just as badly from the drug he takes to combat the disease, which gives him
wild, flailing movements called dyskinesias. These are the devastating
side-effects of L-DOPA, the drug he is prescribed to unlock his frozen limbs.
However, within 90 minutes of taking an Ecstasy tablet, Tim is able to get off
the floor and perform backflips, somersaults and swallow-dives in a gym. The
trouble is, of course, that Ecstasy is dangerous and illegal - a Class A drug
deemed of no therapeutic value.
The transformation is astonishing, but brain scans at Hammersmith Hospital
reveal no changes in the dopamine levels in Tim's brain. Meanwhile in
Manchester a pair of scientists have long been studying ways of treating PD
that do not involve dopamine. Their theory suggests that another brain
chemical, serotonin may be involved. This ties in with Tim's experience as the
main action of Ecstasy in the brain is to release massive amounts of serotonin.
The scientists are sceptical and put forward the possibility that Tim's
experience may be due to 'placebo effect' - that his belief in the pill working
is strong enough to make it happen. The dramatic climax to Tim's journey comes
when he undergoes a two-day trial - on one day he takes a simple pill, on the
other day Ecstasy. On neither day did Tim, or the film crew, know which he had
taken. Comparison of the two days shows an amazing difference. When Tim takes
Ecstasy his movement is measurably smoother and more fluid, with none of the
dyskinesias he normally suffers.
Although this effect has only been demonstrated in one individual, the
scientists agree that it is the best result they have ever seen in the
treatment of PD, and that it is worthy of investigation. It could be that Tim's
extraordinary chance discovery will be a clue towards a new treatment for
Parkinson's Disease.
Nevertheless, no one is suggesting that Parkinson's patients should experiment
with Ecstasy - indeed, it must be emphasised that Ecstasy might be particularly
damaging to those with Parkinson's.
Ecstasy & Agony : transcript
Tim Lawrence seems able to regain mobility using
Ecstasy
BBC2 9.00pm Thursday 15th February 2001
NARRATOR (DILLY BARLOW):
Five years ago at the age of 34 stuntman Tim Lawrence was told he
had Parkinson's Disease, a condition that is slowly freezing his body, but has
left his mind intact. Three years ago Tim found an unusual way of relieving his
symptoms. The trouble is it involves a street drug, which is illegal and
dangerous. This is the story of how one man's discovery could overturn 30 years
of scientific thought and might eventually lead to an entirely new treatment
for Parkinson's.
TIM LAWRENCE: The first time I ever noticed that something was amiss was I was
getting onto a bus and I found that I couldn't manipulate my left thumb very
well and just paid with my right and thought no more of it, but from that point
my left arm started to lose some of its mobility. Then my left leg started to
get the same degree of laziness and slowness to it. I can remember saying to
friends and people around me that if I could get a name for what this is then
I'd know what to fight. I went to see a consultant and I can remember having to
make a, a, a half hour journey back to my Mum's flat and just blinking back
tears and just reeling in shock because I'd got a, I'd got a name, but in my
mind I was going but no, no, I didn't want that name. My whole image of
Parkinson's Disease at that point was just the received image that most of us
get which is just of elderly people having great difficulty dealing with cups
of tea and funnily enough elderly people always offered cups of tea on saucers,
but anyway so my whole world just dropped out.
NARRATOR: Tim Lawrence was diagnosed with Parkinson's Disease in 1994. It's a
condition which slowly freezes the body. One in 500 of us is destined to get
Parkinson's, probably in our sixties, but occasionally much younger and when it
hits the young it can be especially aggressive. Tim is prescribed drugs to
unlock his limbs, but these drugs often produce distressing side-effects:
twitching movements, for which there is little treatment. Science has tried for
years to find better drugs, but it has failed. As yet, there is no cure for
Parkinson's.
TIM LAWRENCE: You, you can make it 5% of your life or 95% of your life. You
choose, and then of course there's, there's things that you have to adjust to
and you know job changes you have to do and jobs you realise that you'll never
be able to do, you know, like bomb disposal.
LYNNE MICHELLE (Friend): The guy I first met I was 17 and this was the coolest
guy to be around because like we'd be in Bayswater in a shopping mall and Tim
would be there like walking down the aisles on his hands and when he'd finished
that he'd be like juggling the baked bean cans or doing Monty Python sketches
at the till and making everyone laugh and constantly, you know, had this aura
about him that was this incredibly physical, funny, inspired and exciting person
and that was Tim.
NARRATOR: Tim worked as a stunt performer for ten years, on the film Braveheart
and other Hollywood movies and on TV shows such as London's Burning. Acrobatics,
martial arts and sky-diving were also part of a very active life. Today there
are times when Tim can barely move. The drugs that make him mobile sometimes
don't work and when they don't it exposes the raw symptoms of his condition. This
is Parkinson's Disease: rigidity, slowness of movement and tremor.
TIM LAWRENCE: Everything in the body will start getting heavier and heavier and
heavier. Eyelids, vocal chords, tongue, everything just, just goes really
heavy. It's like every cell in the body has just had a dead horse attached to
it.
NARRATOR: What is making Tim feel so weighed down is not a problem in his body,
but in his brain. Tim is missing a vital brain chemical, a chemical called
dopamine. Inside one tiny part of his brain the cells which make dopamine are
dying. Without dopamine Tim is becoming paralysed because it is dopamine that
triggers the whole chain-reaction in the brain which tells the body how to
move. Thirty years ago there was no effective treatment for Parkinson's
Disease. Victims were trapped frozen in bodies which could no longer move, but
in the late 1960s science found a way to restore the lost dopamine with a
synthetic chemical equivalent taken in the form of a drug. It was called
Levadopa or L-DOPA for short and it was hailed as a miracle.
PROF. PETER JENNER (King's College, London): The introduction of L-DOPA was
just, just an absolute revolution. People who had been bed-bound for years
suddenly were able to, to get up and walk. They had control of their lives
back, they had mobility, they were able to become integrated back into society
and it really is the sort of discovery, the sort of revolution that has
affected the lives of tens, if not hundreds of thousands of people world-wide.
NARRATOR: For a while L-DOPA magically unfroze Tim too, replacing the lost
dopamine in his brain and helping him move normally again.
TIM LAWRENCE: When I first went on to L-DOPA the first few months of being on
it are just brilliant. You just get this, all this movement back again.
NARRATOR: For a time L-DOPA kicked Tim's system back to normal, but just years
after starting on the drug there are serious side-effects. This is what happens
when Tim takes L-DOPA today. The drug still gives him mobility, but his
movements are no longer normal.
PETER JENNER: The real problem is that later in the illness the drugs don't
work as well as they, they used to in the early stages and one of the common
side-effects is unfortunately the introduction of involuntary movements so
they're, they're mobile, but in fact they have movement that they can't
control. They will get twisting of their limbs and their bodies and our problem
is that we can make them mobile but they then have a degree of mobility which
is of little use to them.
TIM LAWRENCE: This is, this is known as dyskinesias which is, it's, it's to do
with the fact that the, that the chemical dopamine that I'm, that I'm given is
not as subtle as the, as the dopamine that the, the body itself produces. Whereas
normally one could talk and pour liquid out, for example, for, for me to do
that and focus on if I'm experiencing this involuntary movement I would have to
go silent because even the process of talking is using muscles, vocal chords,
these are all demands on the, on the, on the system really.
NARRATOR: Tim can spend half his waking hours twitching uncontrollably and no
one knows quite why the drug has this effect. It is thought that after a while
the brain cannot cope with the way in which L-DOPA floods it with dopamine. In
a healthy person natural dopamine is released in tune with the body's needs. It
is a devastating side-effect which often appears most severely in young
Parkinson's and young people can face decades on L-DOPA. That's why scientists
are so anxious to find something new.
TIM LAWRENCE: I've had a friend's five year old daughter asking her Mum, 'Why
is Timmy dancing?' to which my response was, 'I've got my own internal rhythm,
free form jazz'. I've had another friend's son every time I'd see him he'd come
back with more ingenious ways of keeping me still: nailing me down, sellotaping
me to the chair, how about if I hold you really tightly, and it was, he used to
get quite inventive and I used to be known as wiggling Tim. It is something
though when you have 65 year old women helping you with your shopping. You do
start to see how flexible this thing pride is.
NARRATOR: Few people realise just how many young people there are with
Parkinson's, many of whom will have to cope with the side-effects of L-DOPA for
years. There's long been a need to find something better for them.
PETER JENNER: I mean we might ask how old were you when you got the illness?
MALE SUFFERER: I was 36 when I was diagnosed.
MALE SUFFERER: I was the age of 34.
FEMALE SUFFERER: Yes, I was 32 just.
MALE SUFFERER: Yeah, I was 27.
PETER JENNER: You see I mean this is, this is absolutely sort of classical and
it's…
NARRATOR: In the UK alone there are seven to eight thousand young sufferers.
PETER JENNER: We have a general concept of what causes the illness, but beyond
that we're still really grasping at straws…
NARRATOR: There is still no consensus about what causes Parkinson's. Head
trauma, viruses, faulty genes and toxins in the environment have all been
suggested, but not proved, but what is known is that those who get it when
they're young can get it very badly.
PETER JENNER: Often their disease appears to be very much more aggressive than
the form of illness which is shown by older individuals. The progression of the
illness is more rapid, their response to drug treatment is lost more quickly
and they also unfortunately will develop many of the long-term side-effects of
therapy, such as the involuntary movements, very much more rapidly than you
would see in an elderly population.
MALE SUFFERER: I had Requip which was supposed to replace it.
NARRATOR: Without L-DOPA they cannot move; with L-DOPA many will become
disabled through too much movement and there is yet another problem. The drug
sometimes stops working altogether leaving them completely paralysed. It is a
particular issue for young people as they have to live with Parkinson's for
many years. For 30 years science has struggled to find a replacement for
L-DOPA, or something that makes it work better and most of this work has been
focussed on the belief that dopamine is the sole key to treating Parkinson's. Dozens
of new compounds which affect dopamine levels in the brain have been tried. Some
work in some patients, but to date science has failed to come up with anything
that is better than L-DOPA, or which calms its terrible side-effects, which
makes Tim Lawrence's story extraordinary. For Tim seems to have stumbled by
accident on a drug which tames the involuntary movements caused by L-DOPA. It's
a drug which has never been tried in Parkinson's before, indeed in the
treatment of any physical illness, but it is a drug which has been part of
Tim's life as a young person. Coming out in the open about his discovery could
lead to a completely new approach to the treatment of Parkinson's.
TIM LAWRENCE: Three or four years ago I was in this club with some friends and
I was just suddenly aware that all these dyskinetic movements, I was just
suddenly aware that everything was completely smooth as, as though I, as though
I'd never had the disease in the first place.
NARRATOR: The drug Tim took was Ecstasy, or MDMA.
LYNNE MICHELLE: I remember one particular time at Glastonbury. It was about two
foot deep in mud and he was having a really hard time and this Ecstasy kicked
in with him and I noticed the mobility. I just, I'd often seen it, but this
time it really hit me. I, he, he started ploughing through this mud and charging
ahead and dancing and, and co-ordinating himself really well.
TIM LAWRENCE: We take risks every day of our life. It, it is illegal, but
there's not really a, a punishment out there that could match what I actually
go through myself on a day-to-day basis.
NARRATOR: Within an hour and a half of taking Ecstasy in combination with
L-DOPA, Tim is transformed, not quite into the stuntman he once was, but into
someone confident enough to tackle moves he hasn't tried for six years. What
you're about to see, according to conventional science, is impossible.
TIM LAWRENCE: Today Matthew I'm going to be Olga Korbut. Great, brilliant. Just
to feel that fluidity of movement again. Everything you tell your body to do it
more or less does. It's complete symmetry and fluidity of movement. It's just
an amazing, liberating feeling. I couldn't have done this without being on
Ecstasy because my co-ordination would have been impaired. I may have had the
strength to do it, but the, the signals would have been erratic.
NARRATOR: Tim's discovery is all the more extraordinary because no one has ever
thought Ecstasy could help someone with Parkinson's, but despite the liberating
qualities of Ecstasy for Tim, he knows the drug is not a practical solution for
him in its current form. He takes it mainly when he goes out clubbing, at most
twice a month.
TIM LAWRENCE: I wouldn't want to feel like that all day every day. It's, it's
an unreal state and because of its unreality it's to be enjoyed as a novelty. I,
I wouldn't like to function every day on it.
NARRATOR: The dangers of Ecstasy are now well documented. It is rarely fatal,
but those who take the illegal drug do risk serious long-term harm. It can
cause memory blackouts and depression and research suggests the drug may be
specially damaging to people with Parkinson's. The big question is: might there
be a way to adapt Ecstasy into something that Tim and others with Parkinson's
could safely take every day? Shown the footage of Tim at the gym, scientists at
Hammersmith Hospital were keen to find out more.
PROF. DAVID BROOKS (Hammersmith Hospital): Well like a lot of young onset cases
Tim has got an aggressive form of the disease. In seven or eight years he's now
reached the stage where he's having severe involuntary movements, dyskinesias,
on levels of medication that are required to keep him mobile. One of the major
problems that we're facing in the clinic is that there are no good drugs to
combat this situation. Tim inadvertently has discovered that Ecstasy seems to
work very well for him which is fascinating and we need to find out why that
is.
NARRATOR: The reason Professor Brooks is intrigued is because Ecstasy is
thought to cause virtually no increase in the levels of dopamine, the brain
chemical Tim is missing and certainly not enough to have any effect on
movement. In fact, the main effect of Ecstasy is to cause a massive release in
the brain of a completely different brain chemical, serotonin.
TIM LAWRENCE: I'm 39.
NARRATOR: Both dopamine and serotonin are brain chemicals known as
neuro-transmitters. Neuro-transmitters are chemicals which relay messages
between the brain's ten billion nerve cells telling us how to feel, move and
react. There are at least 300 different neuro-transmitters and each of these
chemicals carry different types of messages between the brain and the body. Dopamine,
as we've seen, is the critical chemical that kick-starts movement. That's why
its loss in Parkinson's has become such a focus for science. High levels of
serotonin, which occur when you take Ecstasy, make you feel happy, euphoric. Serotonin
is not thought by scientists to have anything to do with movement. Professor
Brooks decided to run a series of special tests. Tim's discovery might just be
the breakthrough everyone in Parkinson's has been hoping for, so finding out
how Ecstasy is working in Tim is vital.
DAVID BROOKS: What we thought we might do, Tim, is get you to have two scans
with a tracer called raclopride which measures the levels of dopamine in the
brain and we'd ask you to have one scan when you're not taking any medication
(Right.) and then a second scan after you take some of your Ecstasy just to see
whether that is producing a release of dopamine and giving you the benefit you
experience.
NARRATOR: Tim will be injected with a radioactive marker and then scanned to
reveal if Ecstasy is somehow causing a release of dopamine in his brain, as the
doctors suspect must be the case.
RADIOGRAPHER: …together to me. Designed by Americans so it doesn't work that
well. How you doing?
NARRATOR: So as not to confuse the tests Tim has cleared his body of L-DOPA.
RADIOGRAPHER: The lights are going down Timothy.
NARRATOR: For the first 90 minute scan Tim takes no drugs at all and his body
reverts to the rigid and immobile state of untreated Parkinson's. The following
day, for the second scan, Tim again takes no L-DOPA, but this time took an
Ecstasy tablet before he arrived at the hospital. Tim has never taken Ecstasy
without L-DOPA before and the first big surprise is revealed as Tim emerges
from the scanner.
RADIOGRAPHER: Just swing your legs over the side and sit on the side. That's
it, just have a rest there.
NARRATOR: After the second scan, on the right, Tim is more mobile. Ecstasy
alone has unfrozen his limbs.
RADIOGRAPHER: Now then, can you try wriggling your toe. Bear with me, you come
towards me. (INAUDIBLE REMARK)
NARRATOR: The drug does not give him nearly as much mobility as when it is
taken in conjunction with L-DOPA, but that it gives him any movement is
surprising.
WOMAN: Now, just the finger tapped you know. Quicker than that.
NARRATOR: Until now no one thought Ecstasy alone could ease the paralysing
effects of Parkinson's.
WOMAN: Going to do it together.
NARRATOR: And then comes the biggest surprise of all. Dopamine, the
neuro-transmitter that the entire medical profession believed was the key to
treating Parkinson's, seems to be playing no part in the unfreezing process.
DAVID BROOKS: It's not at all clear why MDMA, or Ecstasy as it's known, should
help his involuntary movements so effectively. There were two possibilities. One
is that it might be stimulating his natural dopamine in some way that helped
the situation. The other is that it might be working by a completely different
route by acting on other chemical receptors. If one looks at his scans on the
screen here one can see the dopamine binding sites in the centre of his brain
before and after he took his Ecstasy and really there has been very little
change, a few percent difference, so he is releasing very little dopamine
because he doesn't have much, having Parkinson's. After he takes his Ecstasy,
so the mechanism of action of the Ecstasy must be via a different
neuro-transmitter system and so we're very keen now to try and find out what
that system is. It may be that we can find a drug that would act on that and
helps him but be potentially far less harmful to him in the long-term than
taking Ecstasy.
NARRATOR: Tim it seems really has stumbled on something new. The question now
is: can science take it any further? David Brooks suggested that two scientists
at Manchester University, Professor Alan Crossman and Dr. Jon Brotchie, might
have the answer. Professor Brooks knew they'd be interested in Tim's case
because for the past 15 years these scientists have been trying to prove to the
world that it is possible to treat Parkinson's with something other than
dopamine. Their mission started when Alan Crossman noticed that dyskinesias,
the involuntary movements caused by L-DOPA in patients like Tim, bore an
uncanny resemblance to an extremely rare condition called hemiballism. This is
hemiballism and it is not caused by anything to do with dopamine.
PROF. ALAN CROSSMAN (University of Manchester): Hemiballism is a fascinating
condition characterised by wild, flailing movements, throwing movements. It was
known to be caused by a small lesion, a destruction, of a tiny region of the
brain called the sub-thalamic nucleus. This little group of nerve cells about
the size of half a peanut.
NARRATOR: The sub-thalamic nucleus sits here deep in the brain. It is close to
the key area where dopamine is produced, but there is no direct connection
between these two structures and until Alan Crossman came along no one thought
the sub-thalamic nucleus was involved in Parkinson's. No one knew this tiny
area of the brain might offer a whole new way of treating the illness.
ALAN CROSSMAN: The sub-thalamic nucleus was regarded as nothing more than a, a
neurological curiosity. The only significance that it appeared to have in brain
function was that once in a blue moon somebody had a stroke in this region and
the consequence was that they had these exuberant abnormal movements:
hemiballism. That was its only function. The only function was to prevent you
having hemiballism. There was no, there was no other purpose for its existence.
NARRATOR: Intrigued by the similarity between hemiballism and the dyskinesias
suffered by patients like Tim, Crossman studied the sub-thalamic nucleus to see
if it might also be involved in Parkinson's. It was something no one had ever
considered before and what Crossman discovered amazed him. The sub-thalamic
nucleus in the Parkinson's brain was hyperactive, quite different than in a
normal brain. It meant this tiny nucleus clearly was involved in Parkinson's. It
was a revelation. Until this point everyone in Parkinson's research had been
focussed on dopamine and the area in the brain which produced it, but Crossman
had found the first direct evidence that a completely different structure, the
sub-thalamic nucleus, which had no direct connection with dopamine, played a
crucial role in Parkinson's too. It was a discovery that has led directly to a
new technique to treat those in whom the side-effects from L-DOPA have become
intolerable. Not a new drug, but surgery. This operation is graphic proof of
Crossman's discovery that the sub-thalamic nucleus plays a vital role in
Parkinson's and it shows that it is possible to control the illness by
manipulating this area of the brain.
(ACTUALITY OPERATION CHAT)
Neuro-surgeon Steve Gill is going to place an electrode in the sub-thalamic
nucleus of 36 year old Simon Burrell who has had Parkinson's for 13 years. If
all goes to plan the surgery should alleviate his Parkinson's symptoms, but it
is risky and it doesn't always work. Sometimes it leaves patients with
depression, speech problems or blurred vision. It can even paralyse or kill.
(ACTUALITY OPERATION CHAT)
To provide vital feedback the patient must be awake and has been off all
medication for 24 hours to expose his raw Parkinson's. At the moment he is
frozen. If the surgeon hits the right place in the sub-thalamic nucleus Simon
will be able to move again. The surgeon advances the probe millimetre by
millimetre and then…
WOMAN: Hold your right hand up. Just make big movements, big (TALKING TOGETHER)
Really wide.
MAN: It's switched him on.
WOMAN: How does it feel?
MAN: Plain sailing from there on.
WOMANL: That's fantastic Simon, well done, that has gone really well, doing
very, very well Simon. Right, big movements.
NARRATOR: This surgery can improve symptoms by up to 70%, for a while at least.
It is not a cure and it remains a last resort. Because of the high risk, Tim is
not prepared to undergo this surgery.
TIM LAWRENCE: This is something I never thought I'd, I'd be using. It's a sort
of adult toddler tippy, something they'd use so they wouldn't spill when
they're going up the north face of the Matterhorn.
NARRATOR It is acknowledged that a new treatment less risky than surgery is
needed desperately and that's why Tim's discovery about Ecstasy could be so
important.
ALAN CROSSMAN: You know haven't you ever noticed the sub-thalamic nucleus…
NARRATOR: Alan Crossman's early work showing the sub-thalamic nucleus was key
in Parkinson's was to change everything. It prompted the Manchester team to
hunt for a drug which could help patients like Tim, a drug which could do the
same as surgery, but be far less dangerous. Jon Brotchie, a pharmacologist,
knew that if he could find out which neuro-transmitter was operating in the
sub-thalamic nucleus there might be a way to manipulate it with a drug which,
like Ecstasy, would bypass the dopamine route, but there are more than 300
different neuro-transmitters in the brain and there was no existing technique
sensitive enough to show which one was operating in such a small part of it.
DR JONATHAN BROTCHIE (University of Manchester): I mean the big problem is that
the sub-thalamic nucleus is very, very small and so exactly, and so you can't,
you, you can't use some of the techniques that you might use if you were
looking at connections between two big pieces of brain.
NARRATOR: It took Brotchie two painstaking years to devise a method he hoped
would reveal which crucial neuro-transmitter was controlling the sub-thalamic
nucleus. Finally he discovered a way to do it. Brotchie took tiny samples of
brain tissue and broke them down into individual cells. The cells were then
bathed in radioactive markers which would stick only to specific
neuro-transmitters. Once the cells were separated back out the radioactive
markers for each neuro-transmitter could be counted and this revealed that the
neuro-transmitter which controlled the sub-thalamic nucleus was one called
glutamate. It soon became clear that a compound which controlled glutamate did
have a small effect on Parkinson's and this was a major breakthrough because it
established the principle that it was possible to treat the illness with a new
type of drug which had nothing to do with dopamine.
JONATHAN BROTCHIE: It was quite a surprise to most of the other people in the
field at the time because there really had been this dogma that, that the only
way of treating Parkinson's Disease was by putting dopamine back.
NARRATOR: But they needed something better than glutamate, so the Manchester
team began looking for receptors for all the neuro-transmitters operating in
the area of the brain which controls movement. There turned out to be dozens
and eventually they discovered that one of them was serotonin, the
neuro-transmitter that floods Tim's brain when he takes Ecstasy. It was a real
hint that serotonin could be involved in movement after all and more proof soon
followed.
JONATHAN BROTCHIE: We did an experiment where we looked at the levels of this
receptor in the brains of Parkinsonian patients who had, had died with very
severe L-DOPA-induced dyskinesias. What we found was that this receptor was
dramatically increased in, in its numbers so suggesting that serotonin was
actually one of the key components of the process that actually leads to the
generation of disconesia.
NARRATOR: It confirmed that serotonin probably was involved in Parkinson's. The
Manchester team was intrigued, but they were still years away from proving that
a drug which affected serotonin could actually work in someone with
Parkinson's. It was still just a theory and then they heard about Tim Lawrence
and his experience with Ecstasy.
PETER JENNER: While we like to think that we all do logically designed
experiments based on real scientific logical reasons for going forward, very
often it's the unexpected that opens new doors and allows new impetus to come
into science and propels us forward.
NARRATOR: Tim appears to be living proof of the Manchester findings, but while
fascinating to science his is only one man's experience. Before any scientist
could commit time and resources to developing a drug based on the properties of
Ecstasy they would need to be more confident that the effect on Tim is real and
not something called the placebo effect.
TIM LAWRENCE: It's just…
NARRATOR: It may seem extraordinary, but the belief that a pill will do you
good can sometimes result in a genuine physical improvement which has nothing
to do with the drug itself. It's caused by the brain deceiving the body. One
placebo study in the US revealed that patients who took sugar pills believing
they were anti-depressants showed almost as much improvement in their condition
as those who took the real thing.
JONATHAN BROTCHIE: The placebo effect is very, very powerful and it's one of
the major factors that needs to be taken into account when determining whether
a drug works or not. For instance, in Parkinson's Disease up to 30% of the
anti-Parkinsonian action of the drugs that are currently available actually
just comes from the fact that the patients are taking a tablet every day. As a
scientists that's the, that's the question I would like answered before we know
whether this is, this is real and worth pursuing further.
NARRATOR: Tim volunteers to take part in an independent two-day trial. On both
days he will be given L-DOPA, but only on one day will he take Ecstasy. On the
other he will take a simple sugar pill. Before the tests start Tim again has to
clear his body of all medication. Once more it reveals how, without drugs,
Parkinson's freezes his limbs. Tim is monitored throughout by neurologist Dr.
Susan Fox, a specialist in movement disorders. The whole test is recorded on
video which Crossman and Brotchie agreed to assess.
DR SUSAN FOX: Can you try and do that for me?
NARRATOR: For the Manchester team, it could provide the evidence that there is
something genuinely worth pursuing. For Tim, it is a moment of truth. Is the
effect of Ecstasy all the work of his imagination, or has he really discovered
something new?
SUSAN FOX: Morning Tim. You clearly haven't had any of your medication this
morning. How are you feeling?
TIM LAWRENCE: Reserved.
SUSAN: Right. Do you, do you feel quite stiff?
TIM: Yeah.
SUSAN: Yeah.
NARRATOR: On both days Tim takes a tablet. On one day it is the simple sugar
pill. The other day it is Ecstasy but they look identical. No one, including
the film crew, Dr. Fox or Tim, knows which is which.
SUSAN FOX: Try and open and close your hand.
NARRATOR: Before the drug has a chance to work Dr. Fox assesses Tim's raw
Parkinson's. On both days he is slow and rigid, particularly on his left side,
which is the most affected.
ALAN CROSSMAN: Yeah he's got major trouble on his left side.
SUSAN FOX: There you go Tim. That's levadopa if you'd like to take that.
NARRATOR: Then at the same time each day Dr. Fox gives Tim some L-DOPA. The
clock is set to zero marking the official start of the test. Twenty minutes
later there is the first sign of a difference between the two days. On Day Two,
on the right, he can already lift his left arm and pick up the mug smoothly.
ALAN CROSSMAN: That's much, much more fluent on his mostly Parkinsonian side,
yeah. Greatly different. Much, much more smooth movement.
JONATHAN BROTCHIE: Uh-huh.
NARRATOR: 90 minutes into the test the L-DOPA that Tim took on both days had
kicked in, but nonetheless it is affecting Tim quite differently. On Day One he
is mobile but has dyskinesias. On Day Two he is also mobile but appears to have
almost no dyskinesias.
JONATHAN BROTCHIE: If that was replicated in him the next time he tried it
would be... clinically significant because you've actually changed that guy's
ability to perform some pretty important tasks, yeah.
NARRATOR: After 2¼ hours on Day One, the effect of the L-DOPA has worn off and
Tim has returned to his untreated Parkinsonian state, but after the same amount
of time on Day Two he is still mobile and moving smoothly. The difference is
particularly marked when Tim is asked to put on a jacket.
SUSAN FOX: Have a go.
TIM LAWRENCE: No I can't.
SUSAN: You can't, OK. Tim, put your coat on and zip it up.
JONATHAN BROTCHIE: Was the best thing I've ever seen in, in a patient, in a,
the best difference yeah. Honestly I think that, that is, that is, you're not
going to show me anything that's better than that. I don't think so. That was
brilliant.
NARRATOR: On Day Two a further twenty minutes later Tim is still mobile and
fluid. By the end of the test Tim has stayed mobile for 30% longer than on Day
One with almost no dyskinesias. By now Tim himself has realised he has taken
Ecstasy because of the effect on his mood. It was later confirmed that it was,
indeed, on Day Two that he took Ecstasy.
JONATHAN BROTCHIE: The reason that we're, we're interested and excited by this
is that we've spent the last well shall we say how many years I don't know
between us, probably between us best part of 50 years trying to understand
dyskinesias and movement disorders generally and the effect that we see here is
probably one of the biggest effects I've ever seen. We've been involved with
several clinical trials for potential drugs that you could add to levadopa and
I've not seen a patient who has shown such a big difference on two films. It
is, as I said, one of the most interesting pieces of footage I've, I've seen
with a potential to develop completely new drugs for Parkinson's Disease.
NARRATOR: News of the outcome of the placebo test reaches the Parkinson's
Disease Society, the national charity which supports the 120,000 people in the
UK who have the illness.
MARY BAKER (Parkinson's Disease Society): The Society of course has to say
quite properly, quite understandably, that it absolutely cannot get in, condone
in any way the taking of an illegal substance, no matter what it can do, but
actually there's a lot more in here for the Society, because the Society I
believe has a moral obligation to ensure that some research follows Tim's
experience, because there just may be in his experience a clue, a vital clue
that is going to help us find a way forward in the better management of
Parkinson's Disease.
JONATHAN BROTCHIE: The, the Tim story's really increased my faith that we can
develop a serotonin based therapy for Parkinson's Disease, although of course
we can't condone what he did and he shouldn't have been taking the drug. He's
given us a clue I think, that's fair to say, and that's a clue that we really
can't overlook if we're going to push forward and make the lives of patients
with Parkinson's Disease better.
NARRATOR: Tim's experience has helped convince the Manchester team that it is
worth dedicating time and money to teasing out exactly how Ecstasy works in
Tim, but it won't be by working with the drug itself.
JONATHAN BROTCHIE: We're not going to be using Ecstasy for, for the research,
we're going to be looking at experimental compounds which mimic individual
actions of Ecstasy. We don't want to use Ecstasy. It's going to have too many
side-effects to be a realistic treatment. If we can dissect out the, the
pharmacology then we can, we can take, if you like, the good out of Ecstasy
without the bad and, and actually develop a treatment based around that.
MARY BAKER: You really cannot ignore what has happened to Tim. You cannot
dismiss it just because it's illegal. Life isn't like that. Life is
complicated. It's not about black and white issues. It's about many varying
shades of grey and I think this, there is evidence here which needs to be
followed up, for the sake of the people living with this extremely challenging
illness.
NARRATOR: Tim's experience is intriguing, but without proper research there
must be caution. That Ecstasy works for him doesn't necessarily mean it could
be developed into a useful treatment for others and there is worry about the
long-term damage Tim could be doing to himself by taking Ecstasy. There is now
evidence that the drug may be destroying what little natural dopamine he has
left in his brain. Many believe that Ecstasy could cause great long-term harm
to anyone with Parkinson's.
PETER JENNER: I can understand fully why, why Tim resorts to Ecstasy because
basically classical medicine has failed him, but is he damaging himself further
for the future? We know Ecstasy in recreational doses can be toxic to remaining
dopaminergic neurons. There's excellent science being done in this area and
what I would hate to happen to Tim is that in fact by having short-term relief
of his involuntary movements he is producing a worse outcome as far as his
Parkinson's Disease is concerned and that his rate of progression might be
enhanced.
STATION ANNOUNCER: The 10.58 to Manchester Piccadilly now boarding at Platform
13, calling at Milton Keynes…
NARRATOR: Tim has now offered to go to Manchester to help with further
research.
TIM LAWRENCE: This, this whole experience has been incredible and quite a
journey. I certainly would never have thought that I'd be having the medical
academia looking over me and interested in something that I just used to look
upon as a recreational thing of a night out. If something could be developed
from this that could be used on a daily basis the change that that would have
on my life, if something like that was available on the market, would be, I
think it would be pretty much total.
PRESENTATION VOICE: If you have been affected by tonight's programme and would
like information or details of organisations that can offer you support and
advice then call the BBC Actionline on 0800 077 077.
Liens et informations supplémentaires -Weblinks:
Parkinson's Disease Society statement:
Parkinson's and the Use of Ecstasy
Recent media reports have highlighted the use of the drug Ecstasy by some people
with Parkinson's. Some reports have suggested that the use of this drug may
offer relief in the symptoms of the condition. The Parkinson's Disease Society
(PDS) does not condone the use of any illegal drug. Although Ecstasy has been
shown to offer some relief to some people with Parkinson's it is against the
law and may have long-term effects associated with its use.
Many issues associated with Parkinson's are never straightforward and can often
be compounded by moral, ethical and emotional dilemmas. Therefore, as the
leading organisation representing those affected by Parkinson's, we are keen
examine all the evidence of Ecstasy use in scientifically and legally
controlled environments.
Click here for more details
on the PDS and its views on the use of Ecstasy.
The PDS has a free helpline, and answers written and email questions.
You are advised if possible to email or send a letter, as the helpline is often
busy.
www.parkinsons.org.uk
Helpline, Parkinson's Disease Society, 215 Vauxhall Bridge Road, London.
SW1V 1EJ
email: enquiries@parkinsons.org.uk
freephone: 0808 300 0303
http://james.parkinsons.org.uk
Further links, easy to use. Funded by NIP, for patient and PD community in the
UK.
www.parkinsonsdisease.com
Awakenings is an open forum, designed and written specifically for all with an
interest in Parkinson's disease (PD), including patients, their caregivers,
primary care physicians, and specialists.
www.netdoctor.co.uk/directory/support_groups/sg.asp?PID=631
Health website offering link to National Drug Helpline and other support
groups.
- The Parkinson's Disease Society of the UK
now has a web site, with a section on research.
- The Parkinson's Disease Society's Young Onset group, YAPP&Rs
- A Doctor's guide to Parkinson's Disease
- AgeNet's Parkinson's Drug Search
- PD Index from
Phil Tompkins
There are also a number of sites where you can access Medline and other deeply
technical medical research information:
- http://www.nlm.nih.gov/databases/freemedl.html
- http://www.nlm.nih.gov/medlineplus/
- http://igm.nlm.nih.gov/