Progress magazine: Summer 2008

Progress I �

Issue 4: Summer 2008

The research magazine of the Parkinson’s Disease Society

Compulsive behaviours and Parkinson’s

Tackling speech problems

How cueing helps walking

Meet... Professor Paul Bolam, Chair of Research Advisory Panel

Spotlight on stem cells

Issue 4: Summer 2008 Summer 2008 :Issue 4Issue 4: Summer 2008 Summer 2008 :Issue 4

Welcome 1from Dr Kieran Breen, Director of Research & Development

Spotlight on... stem cells 2a possible cure for Parkinson’s?

New research projects 7a round-up of Project and Innovation Grants

Themed research 19looking into compulsive behaviours and Parkinson’s

Research Equipment Shopping List 23a PDS branch supporting local stem cell research

Site visit 25tackling speech problems in Parkinson’s

Completed research 27how cueing helps walking in Parkinson’s

Meet... 29Professor Paul Bolam, Chair of the Research Advisory Panel

60 seconds with... 31Bunia Gorelick, Research Grants Manager

Contents

Front cover illustrationJim Dowdalls / Science Photo Library

Embryonic stem cells changing into three kinds of cellsStem cells sit inside a 5-day old embryo (yellow ball in the centre), which is the same size as a grain of sand. They can turn into any of the different types of cells that make up our body (shown in blue, red and purple).

Issue 4: Summer 2008 Summer 2008 :Issue 4

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WelcomeWelcome to the summer issue of Progress, the research

magazine of the Parkinson’s Disease Society (PDS). We have

been as busy as ever in our fight to conquer Parkinson’s. This

issue gives you a snapshot of what’s happening in research and

how we are working hard to develop a cure – that is a treatment

to allow people with Parkinson’s to live a life free from symptoms.

We are delighted to announce that our Board of Trustees have recently approved over

£1.8million of new research projects. These include studies on what causes nerve cells

to die, searching for a cure and better treatments, practical therapy and support for

carers – turn to page 8 to find out more.

The PDS is the largest non-commercial funder of Parkinson’s research in the UK, but

this is only possible because of the generous donations made to the Society. To ensure

your donations are carefully spent on high-quality research, all of our projects undergo

a rigorous vetting system. Professor Paul Bolam, who is the Chair of our Research

Advisory Panel, talks about this on page 29.

To develop a cure for Parkinson’s, the PDS is proactively investing in one of the more

promising routes – stem cells. We support research into both adult and embryonic stem

cells within a strict legal and ethical framework. The PDS has been campaigning hard

on behalf of people living with Parkinson’s to drive forward the research effort in the UK.

The first article in Progress outlines the importance of stem cell research and what it

means for Parkinson’s.

Finally, you may have seen or read in the media about the link between certain anti-

Parkinson’s drugs and changes in people’s behaviours. This side effect of compulsive

behaviours is a real problem for some people with Parkinson’s and can have potentially

life-shattering effects. To address this, the PDS has invested £640,000 into a research

programme on compulsive behaviours. Turn to page 19 to read about one person’s

addiction to gambling and how we are tackling these devastating behaviours.

Dr Kieran Breen

Director of Research & Development

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More than 100 trillion cells pack together to make up

all the tissues and organs in our bodies. Throughout

our lives, these cells are constantly ageing, dying

and being replaced. Each cell works hard to keep us

fit and healthy but sometimes the machinery in cells

can go wrong – they get sick and die.

Parkinson’s arises when nerve cells die in the part of

the brain called the substantia nigra. Once around 80%

of these cells are lost, an assorted mix of symptoms

appear. They affect a person’s everyday activities

– simple things like walking, talking and writing.

Right now, over 120,000 people in the UK are living

with Parkinson’s. There is no cure – that is, a treatment

that allows people to lead a normal life free of all the

symptoms – and most of the causes are unclear. For

that reason, research into Parkinson’s is essential, and

one of the more promising routes is using extraordinary

cells called stem cells.

What’s special about stem cells?Stem cells are exciting because they have the potential

to revolutionise medicine (see Fact box 1). They are like

‘blank’ cells, which can divide forever. We have more

than 200 different types of cells such as nerve cells

and muscle cells in our bodies – and each of these

originates from a stem cell.

Basically, there are two main types of stem cells

– embryonic stem (ES) cells and adult stem cells.

Without them, babies wouldn’t grow and wounds in our

skin wouldn’t heal.

Fact box 1: How stem cells could revolutionize medicine

Research tools

• to figure out how cells work, how humans develop

and how we get diseases

Drug discovery• to find new drugs and check they are safe and

effective

Cell-based therapies• to replace or repair damaged tissues and organs

How could stem cells help people with Parkinson’s?The idea behind healing the brain is simple – we know

that the symptoms of Parkinson’s appear when the

supply of dopamine falls in the brain. So scientists are

figuring out how to turn adult or ES cells into dopamine-

producing nerve cells. These cells could then be grown

in the laboratory and transplanted into a person’s brain.

Once integrated into the brain, the healthy cells would

Spotlight on...

stem cells


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raise the levels of dopamine, allowing the different parts

of the brain to communicate properly again. This would

hopefully ease the symptoms of Parkinson’s.

The idea of using stem cells to treat Parkinson’s is

now becoming a realistic possibility. However, these

therapies are still experimental and under development.

At the moment, it is impossible to predict how long it

will take for a stem cell therapy to become available to

people with Parkinson’s. Also, if a therapy is approved,

it is unlikely to work for everyone but only a specific

group of people. This is similar to how people respond

differently to anti-Parkinson’s drugs.

The PDS knows stem cell science is an extremely fast

moving field that has many hurdles to overcome (see

Fact box 2). So over the last seven years, we have

invested £2million into 16 stem cell projects throughout

the UK. Our scientists are working hard to understand

adult and ES cells so they can potentially harness their

power to treat Parkinson’s.

It is very important that both avenues of stem cell

research (ES and adult) are kept open to move as

swiftly as possible towards developing a potential cure

for Parkinson’s. This is because developments in one

type of stem cell can help bring forward a scientific

breakthrough in another. At this stage, scientists do not

know which type of stem cell, if any, will eventually lead

to a successful treatment or cure.

Getting stem cells from an embryoWhen a sperm fertilizes an egg, a one-cell embryo is formed. Pretty soon, the embryonic cell starts to divide and five days later has grown into a tiny ball of around 100 cells. To give you an idea of size, this embryo is about the same size as a grain of sand (Figure 1). Inside the embryo, there is a tiny clump of ES cells. They are powerful cells whose destiny is to make every cell, tissue and organ in our bodies.

Scientists mainly get ES cells from ‘spare’ embryos that would have otherwise been thrown away. Created in the test tube by in vitro fertilization (IVF), these extra embryos are no longer required for fertility treatment. Some couples, therefore, decide to donate them to medical research. The use of human embryos in UK research is carried out under strict guidelines put into place by an organisation called the Human Fertilisation

and Embryology Authority (HFEA).

Unfortunately, scientists don’t have enough human

ES cells for their research projects, so they have been

looking at other ways of making them.

Getting stem cells from an adultScientists now believe that most of our bodies’ tissues

and organs contain adult stem cells. They are hidden

deep within organs and provide a constant supply of new

cells, such as blood and skin. Acting like our very own

built-in repair kit, adult stem cells replace cells damaged

by disease, injury or everyday wear and tear. Recently,

scientists have also found them in surprising places like

the brain, which is not known to readily regenerate itself.

Compared to ES cells, adult stem cells are less flexible

and somewhat limited in what they do. For example, bone

Fact box 2: Tackling the research challenges

Scientists need to answer questions like:

• what the best source(s) of stem cells is

• how to change a stem cell into a dopamine-producing

nerve cell

• how to grow large quantities of nerve cells

• how many nerve cells should be used in a transplant

• where is the best place in the brain to transplant cells

• how to check that transplanted cells become ‘wired’

into the brain

• how to be certain that transplanted cells make and

release dopamine

• how to stop transplanted cells from dying or growing

into tumours Figure 1 Clump of ES cells sitting in the eye of a needle

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marrow stem cells mainly give rise to the different types

of blood cells. However, scientists are working hard to

find ways of making adult stem cells more versatile.

If they succeed, a person’s blood stem cells might

one day be persuaded to turn into nerve cells. More

research needs to be done to understand how adult

stem cells work and if they could be used in Parkinson’s.

Cytoplasmic hybrids – an answer to the ES cell shortage?Besides getting human ES cells from spare IVF embryos, they could potentially be made by an extraordinary technique called therapeutic cloning (Figure 2). Here a cell, like a skin cell, would be taken from a person’s body. The nucleus, which houses the genetic material of DNA, would then be removed and put into an ‘empty’ human egg from which the nucleus has previously been removed. Scientists would then spark the egg to start dividing until it grows into a very early embryo from which the ES cells are extracted.

To date, scientists have used therapeutic cloning to make ES cells from animal skin cells. In theory, the same could be done with human skin cells but so far this has not been achieved.

At the moment, the big problem is that there are not enough human eggs and embryos to make ES cells for research purposes. One way of solving this is to use eggs from animals and creating cytoplasmic hybrids.

A cytoplasmic hybrid is a cell that consists of elements from an animal and a human. It is created by putting a person’s DNA into an empty animal egg. Nearly all of

the DNA (99.9%) in a cytoplasmic hybrid is human. A tiny amount (less than 0.1%) is animal genetic material. If cytoplasmic hybrids are grown in the laboratory, the ES cells could then be extracted and used for vital research experiments (see Fact box 3).

At the time of publication, the UK Parliament is still debating the Human Fertilisation and Embryology Bill and the use of cytoplasmic hybrids for research. If approved, research using cytoplasmic hybrids will be very tightly regulated. They will only be used as a research tool for experiments in test tubes. Cytoplasmic hybrids will only be grown in the laboratory for a maximum of 14 days. They will not be put inside a woman or animal and scientists cannot create children from cytoplasmic hybrids.

Figure 2 Therapeutic cloning – DNA from an adult mouse cell is being injected into an ‘empty’ mouse egg

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Fact box 3: What would cytoplasmic hybrids be used for?

Understanding Parkinson’s

• helping scientists work out the mechanics behind

the condition – what causes nerve cells to die and

how to stop this from happening

• figuring out how stem cells can change into nerve cells

Drug discovery• finding drugs that are more effective at treating

Parkinson’s or stopping the condition from getting

worse

Drug safety• checking new Parkinson’s drugs are not harmful

before giving them to people

Personalised nerve cells can treat miceAnother advantage of therapeutic cloning is the possibility of making personalised nerve cells. This would help stop transplanted cells from dying (see Fact box 4). New and exciting research has suggested that personalised nerve cells from sick mice appear to relieve Parkinson’s-like symptoms. Researchers from the United States and Japan took skin cells from mice with a Parkinson’s-like condition and injected the DNA into ‘empty’ mouse eggs. They used therapeutic cloning to create ES cells that were then turned into dopamine-producing nerve cells.


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iPS cells – another way of getting ES cells?At the end of last year, two teams of researchers from

Japan and the United States announced an exciting

breakthrough. They had discovered a brand new way

of rewinding time to turn ordinary adult cells back into

‘blank’ stem cells, which appear to be very similar to ES

cells.

The researchers took human skin cells and added just

four genes. This ‘reprogramming’ created a new kind

of stem cell called induced pluripotent stem cells or

iPS cells. They appear to have the potential of turning

into any type of cell without using human eggs or

embryos to do it. What’s more, a few months ago,

researchers announced that they had successfully used

reprogrammed skin cells to form nerve cells that ease

the symptoms of rats with a Parkinson’s-like condition.

Although these are gripping discoveries, some

scientists are remaining cautious. iPS cells are not

identical to ES cells – and any differences need to be

carefully explored. On top of that, there are two major

stumbling blocks that make this approach unsafe

before they could even be considered for use in people.

Firstly, the DNA in the cell must be permanently

changed to trigger reprogramming. At the moment,

scientists don’t know if this causes any long-term

harmful effects. Unlike cells made from ES cells

that have shown to be genetically stable by many

researchers around the world, cells made from iPS

cells might not be stable over long periods of time.

Secondly, the approach uses viruses to carry the genes

into cells, which may cause cancer. Scientists hope to

solve these problems and create safer iPS cells that

could one day be used to treat people.

Can nose stem cells treat Parkinson’s?Along with ES cells, there have also been advances

with adult stem cells. Australian scientists have recently

discovered that human nose stem cells appear to treat

rats with Parkinson’s-like symptoms. The stem cells

were taken from the back of a person’s nose and then

transplanted into the brains of rats. These human stem

Fact box 4: Personalised nerve cells

One of the biggest obstacles in stem cell therapy is

overcoming a process called immune rejection.

The body recognises cells transplanted into the

brain as being ‘foreign’. So it triggers an immune

attack that can cause the transplant to fail and even

endanger the patient’s life. This can also occur

following the transplant of other organs and tissues

in the body. To overcome this, patients who receive

transplants would have to take drugs to suppress

their body’s natural defences. However, these drugs

have side effects and can leave patients vulnerable

to catching dangerous infections.

Personalised nerve cells would be genetically

identical to those already present in the patient.

If these cells are transplanted, it is unlikely that the

patient’s body would reject them. The transplant is

more likely to be successful and the patient could

avoid taking drugs to suppress the immune system.

In theory, personalised cells could be created using

stem cells from:

• adult stem cells

• therapeutic cloning

• induced pluripotent stem (iPS) cells

At the moment, only therapeutic cloning has been

shown to make personalised nerve cells that

successfully treat Parkinson’s-like mice. Scientists

are still trying to develop personalised nerve cells

using the other techniques.

The newly-made nerve cells were genetically matched to each sick mouse. When the nerve cells were transplanted into the mouse from which the genetic material had been obtained, they seemed to improve the symptoms. What’s more, the transplanted cells were accepted by the brain and there were no signs of rejection. In contrast, when the nerve cells were transplanted into a different mouse, which did not have the same genetic material, the cells did not survive and the mice did not recover.

If therapeutic cloning could be repeated in people, it would open the door to potential new treatments that reduce transplant rejection. However, moving science from mice to humans is a massive step and it is unknown

at this stage whether it would work in people.

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cells turned into dopamine-producing nerve cells and

were found to improve the symptoms of rats. This is a

fascinating discovery because it means that adult stem

cells might eventually be used to treat Parkinson’s.

Best research to get the quickest resultsStem cell research is a dynamic and fast-moving field.

Over the last year, there have been many thrilling new

discoveries and scientific developments. All of these

bring researchers another step closer towards

a treatment for Parkinson’s.

The PDS strongly supports research into both adult

and ES cells. We are working hard to drive forward

the research effort in the UK that will ultimately benefit

people with Parkinson’s. But it is important for people

to keep in mind that research is still in the early stages.

At the moment, it is impossible to say which type

of stem cell will give us a treatment for Parkinson’s.

Compared to adult stem cells, human ES cells have

only been studied for a short time. Most laboratories

around the world have only been working on them for

five years. Despite this, a great deal of progress has

been made in a relatively short time.

Each type of stem cell has its own strengths and

weaknesses, and abandoning one of them could

be disastrous. If it wasn’t for research on ES cells,

scientists would not have made the breakthrough

discovery with iPS cells. For this reason, the PDS

strongly believes in keeping all options open, so

that the scientific community has the best research

environment to get the quickest results for people

with Parkinson’s.

Human Fertilisation and Embryology Bill

At the time of printing, the Human Fertilisation and

Embryology Bill has been completing its passage

through Parliament.

The Bill updates the 1990 Act and brings cytoplasmic

hybrids under the same rigorous ethical and

regulatory framework that already exists for human

embryonic research.

This represents a major campaigning success for

the PDS, who along with our members, including our

special research interest group SPRING, scientists

and other research and patient groups, played a

crucial role in building it’s support.

Over the last 18 months, our campaign has involved

direct lobbying of Government ministers and

parliamentarians, securing influence through the

media, submitting evidence to two Parliamentary

committees and contributing to the HFEA’s own

consultation on this issue.

Following this consultation, in January 2008, the

HFEA granted one-year licences to two groups of

scientists to conduct research of this kind. One

of these groups has now successfully created

cytoplasmic hybrid embryos.

Steve Ford, Chief Executive of the PDS said:

“The PDS has worked very hard to campaign, raise awareness and build support for research into cytoplasmic hybrids.

We believe that research should be allowed into all types of stem cells. This gives scientists the best chance for developing a potential cure for people living with Parkinson’s.”


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What causes nerve cells to die?What’s the link between nerve cell death and mitochondria in Parkinson’s?

Lead researcher: Dr Alex Whitworth, University of SheffieldCost: £99,88� over �� months

We know that Parkinson’s is caused by the progressive

death of certain nerve cells in the brain. However,

we still don’t know the reasons why the cells die.

So scientists are working hard to answer three main

questions:

• What causes Parkinson’s?

• Why are particular nerve cells vulnerable?

• How does the disease develop?

By answering these questions, we are optimistic of

finding better ways of treating the condition, and,

ultimately, a cure.

A lot of research suggests that tiny batteries in cells

might play a vital part in Parkinson’s. These batteries

are called mitochondria and they are central to the life

and death of cells (see Fact box 5 on page 8).

Nerve cells are a real challenge for mitochondria. This

is because the cells are very long – up to one metre in

length in humans, and have a high demand for energy.

So the mitochondria have to whizz around different

parts of the cell to supply much-needed energy in the

right place and at the right time.

Dr Alex Whitworth

Our research group is interested in learning how altered fission-fusion of mitochondria is linked to the nerve cell death seen in Parkinson’s. Recently scientists have shown that two genes involved in inherited Parkinson’s, called parkin and PINK1, somehow keep the mitochondria in good working order.

We believe that these genes work together with other parts of the fission-fusion machinery to move mitochondria around the cell. So any defects in the nuts and bolts of the machinery will lead to nerve cell death. Our research project is designed to test this theory. We will do this by performing a series of genetic studies using fruit flies (see Figure 3 and Fact box 6 on pages 8 and 9).

NewThe PDS has recently approved funding for 12 Projects and two Innovation studies. This new research into Parkinson’s costs over £1.8million. The researchers talk to us about their projects and plans. To help us meet these costs, we welcome donations to the PDS’s ‘the next step’ appeal and grants to support individual projects (see back cover).

The mitochondria do this by going through a constant

cycle where they split apart and then come together

again. This cycle is known as fission-fusion. The latest

studies have shown that problems with fission-fusion

mean the mitochondria can’t move around the cell

properly and this triggers the cells to self-destruct and

eventually die.

research Projects

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What key factors are responsible for nerve cell death?

Lead researcher: Dr Frank Hirth, Kings College LondonCost: £�84,�9� over �� months

Parkinson’s develops after cells are lost from the region of the brain that controls movement. These cells produce dopamine, a chemical that enables people to perform smooth, co-ordinated movements. When about 80% of the dopamine-producing cells are gone, the symptoms of Parkinson’s emerge.

We don’t know what causes Parkinson’s but up-to-date research suggests the cell’s mitochondria, together with oxidative stress, seem to be pivotal factors.

Mitochondria (see Fact box 5) are of vital importance and generate energy through a chain of chemical reactions. However, these reactions are never ‘clean’ and produce hazardous things called free radicals (see Fact box 7 on page 11).

Dr Frank Hirth

Too many free radicals are bad for the cell. If they pile

up, they harm the mitochondria and put the cell under

a lot of strain or ‘oxidative stress’. Scientists think this

might be fatal for nerve cells. However, there is a lack of

conclusive evidence and a direct link needs to be proven.

Fact box 5: MitochondriaWhat do they do?

• Mitochondria are tiny batteries that power cells.

• Cells need energy to move, grow and repair.

• Nerve cells need a lot of energy so have lots of mitochondria.

What’s the link with Parkinson’s?• In Parkinson’s, the mitochondria don’t work properly.

• Some people have a faulty component called ‘Complex I’.

• Complex I is a major player in energy production.

• Faulty Complex I is thought to make nerve cells more sensitive to free radicals, which may cause them to become sick and die.

Figure 4 Dopamine-producing nerve cells (coloured green) in the brain of an adult fruit fly

The results from these experiments will help us

understand the link between defects in the way

mitochondria move and nerve cell death in Parkinson’s.

This will help guide researchers to develop new drugs that

may help stop or slow down the death of nerve cells.

Figure 3 Normal eye of a fruit fly (left) and PINK1-parkin mutant (right). A healthy eye is made up of around 800 specialised nerve cells but the mutant eye is much smaller as a lot of the nerve cells have died

Our research group believes that both the mitochondria

and oxidative stress are directly responsible for the loss

of dopamine-producing nerve cells in the brain. To show


Progress I 9


this, our team proposes a series of experiments using

the brains of fruit flies (see Figure 4 and Fact box 6). We

will expose dopamine-producing nerve cells to chemical

and genetic damage. This will cause the mitochondria

not to work properly and lead to oxidative stress. We will

then look at whether dopamine-producing nerve cells in

the fly brains live or die.

If the results from these experiments support our theory,

we will be able to prove that impaired mitochondrial

function and oxidative stress directly cause nerve cell

death. The research outcomes will open doors to the

different pathways involved in neurodegeneration. This

will assist scientists in discovering new ways of rescuing

or protecting nerve cells in people with Parkinson’s.Nicotine-related substances – a potential treatment for Parkinson’s?

Lead researcher: Dr Stephanie Cragg, University of OxfordCost: £��,04� over �� months

Despite having been introduced almost 40 years ago, levodopa is still the most common treatment for Parkinson’s. Although initially very effective, levodopa loses benefit with time and is troubled by side effects. Scientists are therefore keen to develop other treatments with fewer side effects.

We have found that nicotine has crucial effects on the working of dopamine in the normal healthy brain, and nerve cells that make dopamine can react to nicotine.

Our research team is interested in a group of chemicals called nicotine-related substances. We think that these substances may have two possible benefits for nerve cells. They might:

• boost the amount of dopamine being produced to help relieve the symptoms

• protect the nerve cells from further damage – that is,

to stop the progression of Parkinson’s

Our group plans to test whether nicotine-related substances can act on nerve cells and boost dopamine production. We will see if this has any effect in mice with Parkinson’s-like symptoms. Our studies aim to provide a better understanding of how and why this happens. We hope that the knowledge and outcomes from this research will inform the design and development of drugs that mimic the effects of nicotine with minimal side effects.

Fact box 6: Fruit fliesWhy do scientists use fruit flies?

• People and fruit flies share many genes with similar

functions.

• Scientists can easily change (add or subtract) the

genes in flies.

• Each fly only lives for about 100 days, so they can be

studied over several generations.

Adult fruit fly

What’s the link between fruit flies and Parkinson’s?• Each fly only has around 100 dopamine-producing

nerve cells in the brain (Figure 4). By contrast, a person

has millions of cells. Since people and flies share many

genes, they are a great tool for understanding why

nerve cells die as they are easy to study.

• Fruit flies can be created that have some symptoms

like Parkinson’s. For example, trouble controlling

movement, Lewy bodies in the brain and age-related

death of dopamine-producing nerve cells.

As little as £5 a month can help us find a cure for Parkinson’sYou can play a major part in the fight against Parkinson’s.

‘The next step’ is a new initiative that enables people to donate directly to research. By agreeing to make a monthly or annual gift, you’ll be playing a vital role in making the next breakthrough.

Download a Direct Debit form at www.parkinsons.org.uk/donate or call 01753 688 687 (quoting reference Progress)

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How alpha-synuclein and nitric oxide synthase cause nerve cell death

Lead researcher: Dr Richard Wade-Martins, University of OxfordCost: £��,4�� over �� months We would like to thank The George John and Sheilah Livanos Charitable Trust for supporting this project

Over recent years, two big themes have emerged in Parkinson’s research – the role of a protein called alpha-synuclein and an enzyme called nitric oxide synthase (NOS).

Scientists now know that the alpha-synuclein gene is involved in the rare inherited type of Parkinson’s, as well as the more common non-inherited form of the condition. What’s more, abnormal alpha-synuclein protein is a key component of Lewy bodies. These are small round clumps of debris found in nerve cells of people with Parkinson’s.

Scientists are still figuring out why these clumps form and the importance of alpha-synuclein in how this happens. They think it may have something to do with

how cells get rid of old or damaged proteins.

On the other hand, the enzyme NOS influences the amount of stress a cell is placed under. It is important in producing chemicals called free radicals (see Fact box 7). However, when there are too many free radicals the cell is said to be under ‘oxidative stress’. This is thought to damage nerve cells and cause them to die.

Our research aims to study how alpha-synuclein and NOS contribute to the death of nerve cells. We believe that they somehow come together to alter the amount of free radicals.

To investigate their joint role, we plan on growing mouse and human nerve cells in the laboratory. We will turn off the genes for either alpha-synuclein or NOS in these cells. After exposing the cells to a neurotoxin that causes oxidative stress, we will measure the levels of free radicals and NOS activity. Finally, we look at the expression of certain genes and proteins using brain tissue from people who had Parkinson’s and donated to their brains to the Tissue Bank.

We hope that these experiments will help fill some of the blanks in our knowledge. If successful, we will be able to work out how alpha-synuclein and NOS combine to potentially lead to the loss of nerve cells. By targeting specific proteins, we could find more effective ways of treating Parkinson’s.

Dr Richard Wade-Martins

Research in this project uses human brain tissue such as that donated to the PDS Tissue Bank


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Searching for a cure and better treatmentsCan human stem cells repair the brains of rats?

Lead researcher: Dr Maeve Caldwell, University of BristolCost: £��0,�49 over �� months We are grateful to the Medlock Charitable Trust for supporting this project

Stem cell therapies potentially offer great promise to

people with Parkinson’s. The goal of stem cell research

is to replace dead dopamine-producing nerve cells

with new, healthy cells. This would restore the supply

of dopamine in the brain and allow the brain to work

properly again.

Scientists are working hard to establish a possible

stem cell treatment for Parkinson’s. Unfortunately, we

are running into many obstacles. For example, we are

still trying to work out the best source of stem cells,

how to grow large quantities of high-quality cells in

the laboratory and how to stop cells from dying once

they are transplanted into the brain. To tackle these

problems, stem cell research is being carried out in

many different avenues.

Our team plans to study how human embryonic

and fetal stem cells can be used to treat rats with

symptoms similar to Parkinson’s. We will engineer

human stem cells to make a protein called Lmx1a that

appears to influence how the cell behaves. We believe

that it will help human stem cells turn into dopamine-

producing nerve cells. These cells will be transplanted

into the brains of rats with Parkinson-like symptoms.

We will then look to see if there are any changes in the

treated rats symptoms. This will tell us whether the

transplanted cells are having a beneficial effect.

Our team will also design human stem cells to make

other proteins, including those called JBD and Bcl-2.

We believe these proteins will help the dopamine-

producing nerve cells live longer after transplantation.

This project will lead to a major advance towards building

our understanding of how stem cells are changed into

nerve cells and the proteins required to help them stay

alive. If successful, we will establish a way of growing

large amounts of dopamine-producing nerve cells that

live longer when transplanted into animals.

For more on stem cell research and what it means for Parkinson’s, turn to page 2.

Fact box 7: Free radicals

What do they do?

• Free radicals are chemicals that take part in a cell’s

everyday activities.

• Mitochondria make free radicals when they generate

energy.

• The amount of free radicals is controlled by chemicals

called antioxidants.

• Antioxidants immediately ‘mop up’ and neutralise

excess free radicals.

What’s the link with Parkinson’s• Most people with Parkinson’s have high levels of free

radicals in their brains.

• Too many free radicals and not enough antioxidants

places a terrible strain on a cell – it is said to be under

‘oxidative stress’.

• Extra free radicals are thought to lead to nerve

cell death.

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Why does DBS cause depression in some people with Parkinson’s?

Lead researcher: Dr Trevor Sharp, University of OxfordCost: £��,8�0 over �� months

Deep brain stimulation (DBS) is an operation that has striking results in some people with Parkinson’s who are having problems with their current medication (Fact box 8). Unfortunately, DBS causes almost half of people with Parkinson’s to experience unpleasant feelings such as despair and worthlessness. These symptoms resemble clinical depression and are a terrible burden for people with Parkinson’s and their families.

At present, our knowledge of DBS is incomplete. There is no way to pinpoint which people with Parkinson’s might experience depression as a side effect of DBS. We do not know the reason(s) why DBS produces these symptoms or the best way to treat them.

Latest research suggests that stimulating the subthalamic nucleus (STN), part of the brain that is targeted by DBS, appears to affect a chemical called 5-hydroxytryptamine or 5-HT.

5-HT plays an important role in a person’s mood and state of mind. Our research team believe that depression after DBS is caused by changes in the levels of 5-HT.

Dr Trevor Sharp

To conquer this problem, we plan to investigate how

DBS changes the level of this chemical in the brains

of rats who have undergone the treatment. This will

give us a better understanding of what is happening in

people with Parkinson’s. We are optimistic that if our

results are positive, it will help us develop new and

better ways of preventing depression after DBS.

Fact box 8: What is deep brain stimulation?Deep brain stimulation (DBS) is a type of surgery that

can help people with Parkinson’s control their body

movements. The surgery was pioneered in the 1980s

by French scientists and is now carried out in several

specialist centres across the UK.

Although DBS can greatly improve a person’s

wellbeing and ability to carry out everyday activities,

it is not suitable for everyone. Mostly, DBS is

recommended for people who are not responding

well to their anti-Parkinson’s drugs.

DBS involves inserting a thin wire into the brain.

The tip of the wire contains an electrode which is

carefully positioned into one of three parts of the

brain, known as:

• the thalamus

• the subthalamic nucleus (STN)

• the globus pallidus

These are parts of the brain that are involved in

movement. The wire is connected to a device – like

a pacemaker – that is implanted under the skin near

the collarbone. The person with Parkinson’s can turn

the device on and off on a daily basis using a hand-

held programmer or magnet. When it is switched on,

it sends a small electrical signal to the brain to stop

or reduce the symptoms of Parkinson’s.


Progress I ��


How can we improve DBS?

Lead researcher: Dr Ian Stanford, Aston UniversityCost: £�0�,0�9 over �� months

Parkinson’s develops when people lose a lot of the chemical messenger dopamine. This loss affects an area of the brain called the subthalamic nucleus (STN), which plays a crucial role in the control of movement. It causes the nerve cells in the STN to become over-excited and behave unpredictably. People therefore start to experience problems, such as tremors and inability to move – the key symptoms of Parkinson’s.

At the moment, surgery such as DBS is used to ‘calm down’ the over-excited nerve cells in the STN (see Fact box 8). However, DBS involves surgery and researchers still don’t fully understand the reasons why it helps relieve the symptoms of Parkinson’s.

Interestingly, new research has suggested that stimulating another part of the brain, called the motor cortex, might relieve some of the movement problems for some people with Parkinson’s. To investigate this further, we plan to study how nerve cells in the motor cortex and STN talk to each other. We will do this by comparing the brains of rats that are healthy and those that have Parkinson’s-like symptoms.

Our research will help us understand the mechanics of why stimulating the STN provides relief from the symptoms of Parkinson’s. By understanding how the motor cortex might influence the STN, we hope our research will open up the possibility of targeting other parts of the brain, to produce an effect similar to DBS but without the associated side effects.

Discovering drugs that slow down the progression of Parkinson’s

Lead researcher: Dr Oliver Bandmann, University of SheffieldCost: £�84,�8� over �� months

At the moment, there is no cure for Parkinson’s

and existing therapies only ease the symptoms.

Unfortunately, there is also no treatment that can

stop dopamine – producing nerve cells from dying.

For that reason, there is a great need to develop new

medicines that slow down the rate at which Parkinson’s

progresses. This kind of treatment is called a disease-

modifying therapy and our research team is focused on

finding drugs which may have these properties.

Dr Oliver Bandmann

A big problem in Parkinson’s is that the ‘batteries’ of the

cell, called the mitochondria, don’t work properly (Fact

box 5). If the mitochondria don’t work properly, our cells

will die. In some people with Parkinson’s, there seems

to be something wrong with the mitochondria, not only

in the brain, but also in other cells of the body, such as

the skin cells. However, nerve cells are very fragile and

that is why these are the main cells to die in Parkinson’s.

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Our research team plans to use the fact that there are

problems with the mitochondria, even outside the brain,

to discover new drugs that will slow down or even stop

the nerve cells from dying.

We propose to do this by taking skin biopsies from

people with Parkinson’s that carry mutations in one of

the genes associated with Parkinson’s, called parkin. It is

the most commonly mutated gene in people with the rare

inherited form of early-onset Parkinson’s. We will grow

the skin cells in the laboratory and use them to screen

around 2,000 different drugs. These include about 1,000

drugs which are already licensed and in use for other

diseases, but also around 500 natural products and

further substances known to influence brain activity in a

particular way.

Our team will look to see if any of the drugs appear to

repair the abnormal mitochondrial function. We believe

that if the drugs have an effect in Parkinson’s skin cells,

they will hopefully have an effect on nerve cells as well.

Adult zebrafish

After we have shortlisted potentially useful drugs, we

will test their effect on nerve cells in the embryos of

zebrafish. We have chosen zebrafish as their brain

is, in some ways, very similar to the human brain. We

will check to see if these drugs affect the survival of

dopamine-producing nerve cells (Figure 5).

Figure 5 Zebrafish embryos – arrows point to dopamine- producing nerve cells (purple dots)

Together, we hope that our drug screen in skin cells from people with this rare type of Parkinson’s and zebrafish will be a powerful new tool for the discovery of disease-modifying drugs. If we do find a drug that slows down the progression of Parkinson’s, it will enormously help not only people with early-onset Parkinson’s and parkin mutations, but their families as well. Further studies will then be carried out to reveal whether these ‘positive hits’ may also benefit the more common, non-inherited form of Parkinson’s.

A new way of controlling dyskinesia?

Lead researcher: Professor Peter Jenner, Kings College LondonCost: £��,0�� over �� months

Professor Peter Jenner

Levodopa is still the most effective and widely-used drug

to treat the symptoms of Parkinson’s. Unfortunately,

most people who have been taking it for a long time can

experience severe side effects and difficult complications

including:

• ‘wearing-off’ – when the effects of levodopa dwindle

before it is time for the next dose

• ‘on off’ effects – this is when a person’s response to

levodopa begins to fluctuate. They find themselves

switching quite suddenly between being ‘on’ and able

to move, and being ‘off’ and immobile

• dyskinesia or uncontrollable jerky movements

Problems like these are disabling, tiring and painful

for people with Parkinson’s. Tackling them will greatly

improve how people cope with the activities of

everyday life.

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Progress I ��


At the moment, little can be done to relieve dyskinesia.

There are two potential ways of treating this common

side effect. Firstly, to control it after they have already

appeared and, secondly, to prevent dyskinesia from

occurring in the first place. Unfortunately, over the

years, researchers have made no real progress in

developing such a drug.

Our research team believe that we can overcome

dyskinesia – and it is based upon a chance discovery

involving a chemical called nitric oxide. People

with Parkinson’s have high levels of nitric oxide in

their brains. Too much of this chemical affects how

dopamine is released from nerve cells and seems to

damage the brain.

In our laboratory, we have been experimenting with

an enzyme that makes nitric oxide in cells. It is called

nitric oxide synthase (NOS). We were very excited to

find out that drugs stopping NOS, appear to stamp out

dyskinesia in animals with Parkinson-like symptoms.

So we believe that, if these drugs help hamper

dyskinesia in animals, there is a strong likelihood they

may be able to do the same in people with Parkinson’s.

We are now very keen to investigate our discovery

further. Our research team has proposed a series of

investigations to test these drugs in rats and monkeys

with Parkinson-like symptoms. We plan to test if

those drugs can prevent dyskinesia occurring during

levodopa and dopamine agonist therapies. We also

would like to explore the link between nitric oxide,

nerve cells in the brain and dyskinesia. By doing this,

we hope it may reveal important information about

how dyskinesia is caused.

If successful, our project could lead to an effective

drug to treat and/or prevent dyskinesia in animals with

Parkinson’s. Eventually, this would be tested in people

with Parkinson’s. Managing this common side effect

would prolong the usefulness of Parkinson’s drugs and

improve the lives of many thousands of people.

The importance of NOS is also being investigated by

Dr Richard Wade-Martin. See page 10 for details.

Do changes in blood vessels make Parkinson’s worse?

Lead researcher: Dr David Dexter, Imperial College LondonCost: £��4,�80 over �� months

To work properly, the brain need a good supply of blood.

This is essential to feed nerve cells with oxygen and

other nutrients, keeping them healthy and alive. It is the

job of the vascular system to carry blood to the cells.

Dr David Dexter

The vascular system is basically a network of blood

vessels – similar to a collection of pipes. If any of

the pipes get blocked, it affects the blood flow to

a particular path of the brain (Figure 6). A severe

blockage can stop blood reaching the nerve cells,

which eventually die because they are starved of

oxygen and nutrients.

�� I Progress


Figure 6 Network of blood vessels to the brain. Arteries (red) carry oxygen and nutrients to nerve cells. Veins (blue) take away waste products made in cells

We know that a number of conditions, like high blood

pressure and elevated cholesterol, can damage our

blood vessels. On top of that, our western diet does

not help as it is rich in foods high in salt and fat. Salt

raises our blood pressure and fat can build up inside

the walls of blood vessels and narrow them (Figure 7).

All this leads to vascular disease in the brain during

old age. This is dangerous as damaged blood vessels

might leak or blood clots might form, which increases

a person’s likelihood of a stroke.

Recent studies have shown that damage to the brain’s

blood vessels has been found in around 30% of people

who have been diagnosed with Alzheimer’s. Risk

factors, such as diabetes and high blood pressure, are

known to make people more prone to vascular disease.

New research has suggested that people with

Alzheimer’s, who have these risk factors, have a

more aggressive form of the disease as well. Despite

the connection between vascular disease and

Alzheimer’s, little research has been done to see if

damage to the brain’s blood vessels is linked to other

neurodegenerative conditions, like Parkinson’s.

Our research group is interested in exploring this

possibility further. We want to see if the symptoms

of Parkinson’s are only produced by the gradual loss

of nerve cells, or whether in some people, as with

Alzheimer’s, vascular factors influence the progression

of symptoms.

To do this, we plan on investigating the brains of

people with Parkinson’s that have been donated to

the PDS Tissue Bank here at Imperial College London.

Our team will analyse brain tissue using advanced MRI

scanning technology and microscopic examination.

First, we will see if there are any changes to the blood

vessels in the brains of different people. Next we will

look at each person’s medical history, which was also

provided when they donated their brain. For example,

facts like the age at onset of Parkinson’s, response

to their medication, how frequently they fell, plus

treatments for high blood pressure, cholesterol, heart

disease or diabetes.

This will allow us to compare changes within the brain

with the clinical aspects of Parkinson’s and the person’s

other health history. We will then be able to determine

if there is a link between changes in the brain’s blood

vessels and the progression of Parkinson’s.

If our study is successful, we will be able to show

whether damage to blood vessels in the brain may

play a role in the progression of Parkinson’s. On top

of that, we will be able to draw up a set of vascular

risk factors to assess whether a person is potentially

more vulnerable to vascular diseases in addition to

Parkinson’s.

This information might help us treat people with more

appropriate drugs at an early stage. Doctors could

prescribe medicines such as lipid lowering drugs,

which reduce their risk of vascular disease and

possibly slow down the progression of Parkinson’s.

Figure 7 Damaged blood vessel in the brain. Because of the salt deposits (dark purple), the hole in the middle is narrower and carries less blood to the brain


Progress I ��


The effects of falling can lead to both physical and social problems. They can make a person vulnerable to minor injuries and, more seriously, broken bones. The fear of falling again can also give rise to anxiety and a loss of confidence. This has the potential to start a vicious circle as a person restricts their normal everyday activities. The subsequent lack of exercise can make Parkinson’s worse. It stiffens joints and weakens muscles. This, in turn, increases the likelihood of further falls.

For those reasons, there is a great need to find new ways of preventing or reducing falls. When turning round, a healthy person first moves their eyes towards where they want to go, then their head, followed by their body and legs. People use this ‘eyes first’ approach to maintain balance. Unfortunately, we do not think that this happens in people with Parkinson’s.

Until now, there has been no research on how the ‘eyes first’ part of the process is used in someone with Parkinson’s. We suspect that one reason why people with Parkinson’s find turning so troublesome is that the sequence of eye, head, body and leg movement is altered.

Our research team plans to investigate the sequence and timing of the eye, head, body and leg movements of people with Parkinson’s. We will do this as they turn both during sitting and standing. We think that the head and body may move together, as a block, and this frequently ends in falls. To help prevent falls, we believe that it will be possible to separate the eye and head movements in people with Parkinson’s. This could be done in response to a cue.

Practical therapy and support for carersHow to stop people with Parkinson’s from falling during turning

Lead researcher: Professor Ann Ashburn, University of SouthamptonCost: £��,8�� over �8 months

One of the most challenging movement problems in

Parkinson’s is turning. This can have a huge impact on a

person and how they go about their everyday activities.

For example, not being able to turn or roll in bed makes

sleeping very difficult. Also, trying to turn when standing

or walking can trigger freezing and even falling.

Loss of balance and falling is a great problem for most

people with Parkinson’s. As the symptoms progress

and different muscles become affected, falling down

becomes increasingly common. A stooped posture,

rigid muscle tone and freezing all contribute to the risk.

Around two-thirds of people living with Parkinson’s will

have fallen in the last 12 months, and these people are

very likely to fall on a relatively regular basis.

Avital gift

PDS Tissue Bank

The projects on page 10 and 16 use human brain

tissue. This research only happens because

people with and without Parkinson’s generously

donate their brains.

The PDS Tissue Bank collects and provides brain

tissue to researchers around the world.

Help us drive forward towards a cure for

Parkinson’s - donate your brain as a vital gift.

(See the back cover for more details).

�8 I Progress


We hope the outcomes of the research will help answer

questions about how movement changes in people

with Parkinson’s. The results from the study may guide

the development of treatments that help reduce the

number of falls associated with turning.

Can the stress of caring be reduced by cognitive-behavioural therapy?

Lead researcher: Professor Richard Brown, Kings College LondonCost: £��,�� over �0 months

Family and friends who care for people with Parkinson’s

play an essential and much-needed role. Over time,

however, the physical and emotional demands of caring

can affect the carer’s own health and wellbeing. This

impacts on the individual’s ability to provide care to the

person with Parkinson’s.

There is a lot of research that says giving extra

assistance and support to carers can reduce the level

of stress and burden that they experience. One type

of treatment that has been shown to work is called

cognitive-behavioural therapy (CBT).

CBT is a common treatment delivered by clinical

psychologists. It is used to improve a person’s state

of mind by changing how they think and what they do.

These changes can help the person feel better and

cope with stressful situations.

Our research group has developed a form of CBT that

has been tailored to meet the needs of Parkinson’s

carers. In an earlier PDS-funded study, we successfully

showed one-to-one CBT can help reduce the stress

of long-term caring. Unfortunately, there is a shortage

of clinical psychologists in the NHS. This means that

this type of CBT is unlikely to be available to the high

number of carers that need it.

To address this, we propose to develop a new package

of CBT that can be delivered to larger numbers of

Parkinson’s carers by a Parkinson’s Disease Nurse

Specialist. We will also carry out a controlled trial to

test how effective CBT is in reducing a carer’s distress

and burden. If we can show that the treatment is

effective, it would support making CBT more widely

available on the NHS and help many Parkinson’s carers.

Professor Richard Brown

The PDS has approved two new Innovation Grants:

What happens in the cell when PINK1 gene is mutated?

Lead researcher: Professor Anthony Schapira, University College LondonCost: £�0,000 over �� months

How effective are different cueing devices for people with Parkinson’s with gait initiation difficulties?

Lead researcher: Professor Jim Richards, University of Central LancashireCost: £9,9�9 over �� months


Progress I �9


Over the last few years, research findings have

strengthened the link between some Parkinson’s

medicines and a change in people’s behaviour.

These changes are known as compulsive

behaviours and they are a potential side effect of

certain drugs – mainly dopamine agonists.

Dopamine agonist is a class of drug that treats

Parkinson’s by mimicking the effect of dopamine in

the brain. At the moment, scientists think that up to

14% of people with Parkinson’s taking dopamine

agonists experience some problem with compulsions. If

untreated, they can escalate and lead to uncontrollable

addictions that devastate people’s lives.

Little is known about what goes wrong in the brain to

trigger compulsive behaviours, so research is urgently

needed to figure out:

• the causes

• how to treat those affected

• how to stop them happening in the first place by

understanding who is most at risk

A compulsive behaviour is when a person is

unable to resist an impulse or temptation. The

person can’t stop themselves from doing an

activity repeatedly, excessively or obsessively.

What kind of compulsive behaviours are seen in Parkinson’s?Dopamine addictionSome people with Parkinson’s become addicted to

their dopamine replacement drugs. Here, the addiction

is so powerful that they start taking more and more of

the drug – exceeding the dose prescribed to control

their movement. This happens even though they are ‘on’

and experience severe dyskinesia (involuntary jerking).

People may also have very bad mood swings throughout

the day. These can vary from feelings of depression,

irritability and anxiety when they are ‘off’, all the way to

euphoria and hyperactivity when they are ‘on’.

Themed researchCompulsive behaviours and Parkinson’s

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�0 I Progress


Compulsive gambling, shopping and eating, and hypersexualityUnlike dopamine addiction, people can develop other compulsive behaviours by simply taking standard doses of certain dopamine agonists. These behaviours can be expressed in a number of different ways:

• a failure to resist gambling

• an irresistible need to buy things

• binge eating large amounts of food in a short space of time

• a pre-occupation with sexual thoughts or inappropriate sexual behaviour

• an obsessive fascination with hobbies and repetitive activities such as cleaning, collecting or sorting things

In a lot of cases, the behaviour is out of character for

the person. Unfortunately, the consequences can be

very dramatic and bring about terrible work, social and

financial problems.

Patricia’s story:my addiction to gambling

My Parkinson’s was diagnosed 12 years ago, when I

was in my early 40s.

At first, I was prescribed bromocriptine and levodopa,

but really struggled to control my movements. So my

consultant changed my medication regimen, putting

me on a dopamine agonist. I was warned that I might

experience hallucinations as a side effect and this

concerned me. I remember that when I picked up my

drugs, I talked to the pharmacist about my fear of

getting hallucinations. But he said not to worry – that

hallucinations were way down the list of side effects, and

I was more likely to feel nausea.

After taking my new drugs, my behaviour started to

change – I began to place small bets on the internet.

Eye-catching ‘pop-ups’ advertising gambling websites

would appear and I’d find myself clicking onto the links and

betting money. Before I knew it, I became a regular user of

more and more websites. Strangely, if I lost money, I wasn’t

bothered – I felt compelled to carry on and on.

A couple of years later, I visited my neurologist. I

remember telling him that although my Parkinson’s

symptoms were very well controlled, I was worried, as I

felt something wasn’t quite right. I clearly recall asking

him if there was a possibility that my behaviour had

anything to do with my medication or my condition.

But my neurologist said no and nothing was done.

As time went on, my behaviour worsened. I feel bad to

say this, but I found myself becoming more and more

devious. I even used my daughter’s credit card without

her knowing and took out loans behind my husband’s

back. Slowly but surely, my debts piled up, till I could no

longer ignore the alarm bell ringing loudly in my head.

Finally, I shared my fears and problems with my

Parkinson’s nurse. She was great and linked my

obsession with gambling to my medication. So I have

now changed my drugs. I feel like a great weight has

been lifted from my shoulders, and my behaviour is

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Progress I ��


Compulsive gambling has had a truly devastating effect

on my life – as well as the lives of those I love. Without

knowing it, and without anyone recognising it - I turned

from a person who enjoyed the occasional game of

bingo, to an addict who gambled in secret and mounted

many thousands of pounds of debt.

PDS funding the research gapSo far, research into compulsive behaviours has focused

on describing the different types of behaviours and

their effect on people with Parkinson’s. However, many

people with these problems do not receive proper help.

One reason might be that people are unaware that their

changes in behaviour are related to their medication.

Alternatively, they might be too embarrassed to

mention it to their doctors. Also, some doctors might

not be aware of how common these behaviours are, so

do not ask their patients if they are experiencing such

side effects.

Now is the time to raise awareness of this condition

among healthcare professionals, and people with

Parkinson’s and their families. For this reason, the PDS

is bridging the knowlege gap by investing £640,000 in

a large-scale research programme. It will investigate

compulsive behaviours in people with Parkinson’s who

are taking dopamine agonists. The programme consists

of two parallel and complementary studies carried out

by Dr Paola Piccini from Hammersmith Hospital and

Professor Anthony David from King’s College London.

PDS-funded research into compulsive

behaviours aims to answer questions like:

• why certain people are affected

• what is happening in the brain

• what is the best way to treat the problem

What risk factors cause compulsive behaviours?

Lead researcher: Dr Paola PicciniInstitution: Imperial College LondonCost: £��0,��9 over �� months

Our research group is trying to uncover what

risk factors make some people more prone to

compulsive behaviours than others.

We believe that a person’s personality and their attitude

towards risk and reward are very important. Also, we

think that compulsions are triggered when the brain’s

pleasure centres are stimulated too much and become

over-excited.

To test this, the first part of our study investigates the

psychological factors associated with compulsive

behaviours. We are doing this by using questionnaires

to ask around 100 people with and without Parkinson’s

about their attitudes towards gambling, spending,

medication-taking, sexual activity and binge eating.

After we collect and analyse this data, we will see

if there are certain personality traits that are more

common in people with Parkinson’s who either have or

go on to develop compulsions. In the future, we might

be able to use these traits to identify those who may

have a higher risk of developing the behaviours.

During the second part of our study, we plan to

compare the activity of the brain in people with

Parkinson’s who do and do not display compulsive

behaviours. To do this, we will use modern imaging

technologies to look at the brain. As we scan the

brains, we will show people rewarding or pleasurable

images, such as money, appetising foods and

dopamine medications. We will then look at the areas

of the brain thought to be responsible for addiction and

see if there is any difference.

We are optimistic that our research will provide a better

understanding of why some people with Parkinson’s

develop compulsive behaviours. By investigating

potential causes for these problems, it will help doctors

identify at-risk people, and tailor their advice about

medications. It may also lead to ways of stopping

these problems getting worse or even preventing them.Doctors Kit Wu (left), Marios Politis, Paola Piccini and Sean O’Sullivan

�� I Progress


PDS-funded Senior Research FellowshipComplementing the new research programme,

the PDS has already awarded a Senior Research

Fellowship to Dr Iracema Leroi, a consultant in old

age psychiatry and specialist in the mental health

of people with Parkinson’s.

Dr Leroi is also trying to determine which risk

factors might predispose someone with Parkinson’s

to develop compulsive behaviour. However, she

is using laboratory-based behavioural tasks on

people with Parkinson’s that either have compulsive

behaviours or apathy.

Dr Leroi will see how being ‘on’ and ‘off’ Parkinson’s

medications might affect decision-making and risk

taking during certain thinking tasks.

How can we manage compulsive behaviours?

Lead researcher: Professor Anthony DavidInstitution: King’s College LondonCost: £��,�� over �� months

Our part of the research programme investigates

different ways in which people with Parkinson’s

and their carers can manage their compulsive

behaviours more effectively.

One thing that we often hear is that people with

Parkinson’s and their carers find it difficult to ask for

the help they need. We think that having an ‘advocate’,

whose role is to do this, might be very beneficial. We

would like to see if the Parkinson’s Disease Nurse

Specialist (PDNS) can fulfil this role.

In our project, around 40 people with Parkinson’s

and their carers will have a dedicated PDNS, who

has experience and skills in mental health, allocated

to them. Our research will compare people with

Parkinson’s who have access to a dedicated PDNS

with those who don’t.

The PDNS will work with them to find better ways of

managing their behavioural problem using existing

services such as the local community mental health

team, the GP and social services.

The PDNS will also carry out a nurse-led psychosocial

treatment to help manage the person’s compulsive

behaviour and improve the burden on their carer. This

includes optimising medication, looking at beliefs and

attitudes, things that seem to ‘trigger’ compulsions,

and working out coping strategies for both the person

with Parkinson’s and their carer.

If such a treatment does prove to be valuable, it will

have implications for broadening the training of PDNSs.

It will also support the case for having more PDNSs

working with clinical teams looking after people with

Parkinson’s throughout the country.

Dr Iracema Leroi


Progress I ��


What is the Shopping List? Running for 15 years, the Research Equipment

Shopping List has grown in popularity with

researchers and branches alike. PDS-funded

scientists, who require extra equipment for their

projects, apply to place items on the scheme.

Requested items can range from £50 all the way up

to £5,000. The Shopping List is circulated to over 330

PDS branches and support groups throughout the UK.

Each branch then decides if they would like to take

part. If so, they can choose which research project to

support and what piece of equipment to buy. This is

just one of the many ways that branches can support

researchers.

“It is a way for PDS branches and support groups to get involved in research. They help by raising money to buy much-needed equipment for scientists to carry out their everyday work.”

Trish Hadfield, Research Grants Officer

Last year, the Shopping List helped 30 different

research groups across Scotland, England, Wales

and Northern Ireland. Collectively, branches and

support groups kindly donated over £71,000 worth of

equipment to laboratories.

PDS Edinburgh Branch supports local researchOne scientist who has benefited from this generosity

is Dr Tilo Kunath, a PDS Research Fellow, at the

University of Edinburgh. Dr Kunath and his team are

studying how certain genes and chemicals can turn

embryonic stem cells into nerve cells and tissue. After

requesting an electrophoresis tank, the PDS Branch in

Edinburgh stepped in to help.

“People like to see that something positive is being done – it’s good for people in Scotland to give to research in Scotland. It gives a sense of ownership and an opportunity to engage with the researchers.”

Patrick Mark, Chairman of the PDS Edinburgh Branch

The new tank is already being put to good use by the

team:

“We use the tank on a daily basis to separate bits of DNA on a gel with an electric current.

“The DNA contains the genes we are interested in. They appear as bright fluorescent bands, which we cut out of the gel.

“We then separate the DNA from the gel and eventually put the pure DNA into embryonic stem cells.

“This is a vital procedure in our research programme. By doing this, we hope to find genes that instruct stem cells to turn into nerve cells.”

Dr Tilo Kunath

Research Equipment Shopping ListHow PDS branches and support groups are helping researchers

Dr Kunath (right) with his research team

�4 I Progress


This is the second item to be donated to the team by the PDS Edinburgh Branch. Earlier last year, they received a brand new centrifuge. What’s more, these generous donations have come at an ideal time for Dr Kunath…

“I’ve just started my own research group, so suddenly there were four people trying to use one very old electrophoresis tank and a centrifuge borrowed from another laboratory.

“Now we have two modern pieces of equipment that really make a difference. Our research moves much faster – the team can work more quickly and efficiently.”

Dr Kunath

Although a single item may not cost a great deal, it can make a huge difference to the researchers. Dr Kunath and his team will no longer have to queue to use equipment shared with other laboratories. Also, the research apparatus is good value – it lasts for many years and can be used in hundreds of projects.

“The Shopping List is great because it allows members to see where their money is going and how much of a difference it makes to research into Parkinson’s.”

Patrick Mark

Not only does the Shopping List provide important equipment for PDS-funded projects, it also helps build relationships between scientists and people

with Parkinson’s.

“For us, it’s a two-way process that nurtures links with local researchers.

“It’s important for researchers to meet and learn from people living with Parkinson’s, as well as providing opportunities for the scientists to explain their research and how the project is progressing.”Patrick Mark

Electrophoresis tank

Get involved!To find out more about how you and your branch

or support group can help researchers like Dr

Kunath, please contact the PDS Research &

Development team.

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Bands of DNA (orange) on a gel


Progress I ��


with Dr Ho and her team, who gave them a tour of their research facility, a presentation about their work so far, and an opportunity to ask lots of questions.

Can hearing your own voice differently help with speech problems?In this study, Dr Ho wants to know if changing how a

person with Parkinson’s hears their voice while they

speak has any impact on their speech problems.

This approach has proved successful in treating people who stutter, but researchers are not sure how it works. They think it may involve the area of the brain called the basal ganglia. It is the main part of the brain affected in Parkinson’s, and is primarily responsible for the timing and control of movement.

Dr Ho’s team are using special computer software to manipulate the pitch and/or timing of how people hear their voices as they are speaking. To do this, research participants read a variety of different passages into a microphone. The sounds are fed into a computer programme which either delays the vocal feedback (giving an echo effect), or adjusts the pitch to produce a high squeaky or deepened version. This computer

What’s it all about?In Parkinson’s, the ability to speak clearly and

fluently is often affected at some stage as the

condition progresses.

“We know that around ��% of people with Parkinson’s struggle with their speech. Problems include vocal blocks, difficulty in starting speaking, syllable repetition and acceleration of speech rate once they get going.

“At the moment, treatment options such as medicines and surgery are very limited. And unfortunately, they often don’t work.

“My research team is keen to find other ways of tackling speech problems in Parkinson’s.

“We know that techniques that use the senses, like touch, vision and hearing, have worked in people who stutter.

“Our project looks at using similar techniques to help people with Parkinson’s.”

Dr Aileen Ho, Lead Researcher

The PDS awarded Dr Aileen Ho £121,512 to carry out a three-year project on speech problems in Parkinson’s. One year into the research, a group of Research Network members and PDS staff went to visit the University of Reading to find out more about the project and how it’s going. They spent the afternoon

Site visitTackling speech problems in Parkinson’s

�� I Progress


modified version is then played back through the

participant’s headphones while they continue to read.

One of the research participants, Ann, who also

attended the site visit, recalled “the funny sensation of perceiving the delay” in her hearing. By analysing

the recordings, the researchers hope to reveal the best

levels of pitch and delay to control speech.

Results so far“We are still assessing if these techniques could help control speech problems for some people with Parkinson’s.

“Like Parkinson’s itself, speech control varies hugely from person to person. We are finding that different people respond to individual sound stimuli.”

Dr Ho

Looking to the futureThe researchers hope that the outcomes from this project may eventually contribute to the development of a novel hearing-aid type of device. By altering how people hear themselves, it would take all the strenuous work out of speech. So instead of having to concentrate extremely hard to overcome speech difficulties, simply hearing your own voice in a different way may improve speaking.

Who went and what they saidSite visits play a crucial role in helping us build

relationships between PDS members and researchers.

They also provide an excellent opportunity for everyone

to share experiences and ideas.

“Like all the other visits I have attended, it was an enjoyable day. It provided an opportunity to meet some very interesting people and visit a grant-assisted research facility.

“It is good to see, at first hand, the practical work the Society initiates for the benefit of its members.”

Graham, Research Network member

“Because I have Parkinson’s, my voice has recently become quieter, I have been referred for speech therapy and am interested in understanding what can be done to improve voice volume and intelligibility.”

Terry, Research Network member

Although this research is still in the early stages, the

preliminary findings and the potential for the future

were discussed.

“I learnt that some treatments help voice production. In particular, frequency-altered feedback, where the voice can reach high ‘Mickey Mouse’ sounding levels, worked for some people.”

Will, Research Network member

Dr Ho (centre) with PDS members on the site visit

“Obviously we hope this work will lead to some form of device, which will help those whose voice-brain hearing loop is not functioning properly.”

Len, Research Network member

Get involved!To find out what PDS-funded research is going

on near you and get involved in a site visit, please

contact the Research & Development team.

Please note that places on site visits are limited

and allocated on a first come, first served basis.


Progress I ��


Cueing helps walking in Parkinson’s

Does cueing improve walking in people with Parkinson’s with cognitive problems or dementia?

Lead researcher: Professor Lynn Rochester, Glasgow Caledonian UniversityCost: £8,�84 over six months

What it’s all aboutDespite current drugs and surgical treatments,

Parkinson’s will eventually lead to problems in

movement. People develop stooped posture and rigid

muscle tone which have a huge impact on everyday

activities such as walking, turning in bed and rising

from a chair.

If left unmanaged, these mobility problems can worsen

and increase the likelihood of falling and serious injury.

They can affect people’s physical, emotional and social

well-being. Someone with Parkinson’s can end up

losing their confidence and independence. This, in turn,

increases the burden and strain on carers.

One way of managing walking problems is by

physiotherapy. In particular, responding to sound or

image prompts can help overcome mobility issues.

Research has shown that these cueing techniques

can benefit people with Parkinson’s in the short term

by improving the pattern of how they walk (this is also

known as gait). Cues can help to start walking, and

improve the speed of walking, by influencing step

length and step number.

The point of our studyAlongside the physical changes in movement, Parkinson’s may also lead to a variety of other symptoms, such as changes in cognition or one’s ability to think, reason and remember. Cognitive problems mean that a person may:

• think slower

• take longer to make sense of information or problem solve

• find it difficult remembering where and when particular events occurred

When cognitive problems become very severe, they can lead to dementia.

Our research group wanted to investigate whether cueing was a feasible option for a specific group of people with Parkinson’s – those who also have cognitive problems or dementia. We wanted to test if listening to an auditory cue could improve walking in participants who also have trouble thinking, reasoning and remembering, or dementia.

Completed research

�8 I Progress


What we didOur team carried out a small study on nine individuals

with Parkinson’s who also had mild cognitive problems

or mild dementia. We looked at how these people

walked with and without auditory cues during two

different tasks.

The first task involved the person walking in a straight

line. In the second task, the participant did the same

thing as before but had to carry a tray with two cups

of water while walking.

The two tasks were carried out with and without

auditory cues. A metronome – a device that makes a

rhythmical clicking sound – was used to produce the

auditory cue. It provided a steady beat for stepping.

The participants were asked to use the cues in two

different ways when they were walking. They were

asked to:

• walk with the cue by stepping in time to the beat

• walk with the cue while hearing the command

‘take a big step in time to the beat’

A long carpet that records footsteps was used to record

the walking speed, step length and step frequency. Our

team compared and analysed the walking pattern of

each participant.

What we discoveredOur results show that auditory cues improved walking

for individuals with Parkinson’s who have mild cognitive

problems or dementia in both tasks. We also found that

people were also able to use the cues easily. What’s

more, the participants who followed the rhythm of the

cue and heard the command ‘take a big step in time to

the beat’ had the greatest improvement.

What happens next…PDS Innovation Grants are designed to support

small studies that open up new research avenues

in Parkinson’s – so if the results are positive, the

researchers can apply for more funding to carry

out bigger trials.

Our project has produced very good data, which we

are going to use to support another grant application.

We would now like to carry out a larger trial to test if

auditory cues can improve walking in a larger group of

people with Parkinson’s who have cognitive problems

or dementia. This will offer the potential to develop

cueing guidelines and specific exercises that people

can practice in their own homes.

How this helps people with Parkinson’sOur research has the potential to greatly increase the

physical, emotional and social wellbeing of people with

Parkinson’s by improving their walking and reducing

falls. This would have a major effect on their quality

of life – allowing individuals to carry out everyday

activities and lessening the load on carers.

Unfortunately, there are currently no cueing guidelines

for therapists who treat people with Parkinson’s that

also have cognitive problems or dementia.

Professor Lynn Rochester added:

“Little work has been done to develop therapies that improve or maintain safe and independent mobility for people with cognitive problems or dementia.

“We are very keen to address this gap by applying our considerable research experience.

“Simple easy-to-use techniques, such as cues, are particularly beneficial. This is because people can use cues in their homes and tailor them to meet their own needs.”


Progress I �9


The Research Advisory Panel (RAP), a diverse

group of 36 research experts and members of the

Research Network, helps the PDS decide which

projects to fund. We recently caught up with the

Chair, Professor Paul Bolam, for an insight into his

role and how it all works.

Do members of the PDS get involved?Members are involved through the Research Network.

When RAP meets, someone from the Research Network

talks about each project application, and tells us if they

think it’s value for money. For me, this is very important

– hearing what the PDS membership would like funded.

Also, I get to meet people with Parkinson’s and their

carers. It’s very important for scientists to meet the people

who inspire the research, as they are what it’s all about.

The PDS funding process

New research is funded

PDS advertises for research proposals

Applications evaluatedStage 1: International peer reviewStage 2: RAP assessment

PDS Board of Trustees approve

Getting to know you

As a child, what was your dream job?Well, I started off wanting to be a tram driver!

And, if you could go back in time?I would like to see dinosaurs ... I could just watch

Jurassic Park ... but real dinosaurs would be pretty good.

If you went into space what would you take?I would take my garden – so it would have to be a big

spaceship!

What drew you to research?Ever since I was a schoolboy, I remember wanting to be

a scientist. I can actually recall telling a friend, while we

were walking to the rugby field, that I was going to be a

research scientist when I grew up! Many years later, at

university, I developed a real passion for pharmacology

– that’s understanding how drugs work.

Why is it important to have a RAP?Well, the PDS is the leading non-commercial funder of

Parkinson’s research in the UK. Since the Society gives

so much money, we must make sure that it’s going

to the right places. It’s important to have a strict peer

review system with independent experts. They can help

assess whether an application is good quality research

and whether the PDS should fund it.

How does the PDS decide which projects to fund?The proposals need to stand out – it needs to be

a strong idea. New projects have to fit in with the

priorities of the PDS. The science must be high quality

and really benefit people with Parkinson’s, either in the

shorter or longer term. It has to be right. If it’s not right,

then we just don’t fund it.

Meet…Professor Paul Bolam Chair of the Research Advisory Panel

�0 I Progress


The other big thing is the work on genetics, where

several rare types of inherited Parkinson’s have now

been identified. Although this only affects a tiny

proportion of people with Parkinson’s (up to 5%),

knowing how molecules are changing may give us

insights into what’s going wrong with the more common,

non-inherited Parkinson’s. Professor Nick Wood at

University College London has made a lot of those

discoveries, including identifying the PINK1 gene, and is

well supported by the PDS.

Which areas of Parkinson’s research are particularly promising at the moment?Right now, the hot topics are genetics and stem cells

– but it’s difficult to know what they will produce as

they are both at an early stage. I actually think the most

important thing is a neuroprotective therapy, but for this

kind of therapy to be useful, we need an early diagnosis

of Parkinson’s.

I believe you have to support a wide variety of research

projects, which the PDS does. By doing that, it may lead

to an exciting scientific breakthrough or it may simply

add new grains of sand to the beach of knowledge.

Are there ever differences of opinion between the scientists and Research Network members?Sometimes – the Research Network may look at a grant and decide that the topic is important to people with Parkinson’s. Then the researchers might assess the same grant and say the research plan is poor. It’s a good thing to hear what’s very important to people with Parkinson’s. However, it’s also important to look at the project plan and design. We cannot fund the project if it’s not well constructed and we do not believe the people can do it.

What does a Chair do?I’m like an enabler; I facilitate discussion and ensure there is fair play at all times. So that means everybody in the meeting has an opportunity to speak about the project applications and feel confident that their opinion is taken into account. I then make sure that the recommendations put forward to the Board of Trustees reflect the true wishes of RAP.

What have been the most exciting recent developments in Parkinson’s research?I think a major development has been deep brain stimulation (DBS). That was really a fantastic thing to see – all these different strands of research coming together and leading to a therapy which has benefited around 40,000 people across the world.

What the PDS is doing

DBS and the PDSDBS can hugely help certain people with Parkinson’s.

Unfortunately, access to funding varies across the

UK. So the PDS is proactively campaigning for equal

access regardless of where people live.

We have also invested £250,000 in a ten-year study

called PD SURG which began in 2002. It is looking at

the long-term benefits and safety of DBS for people

with Parkinson’s.

Genetics and the PDSThe PDS recognises that studying the contribution of

genes to Parkinson’s is crucial for developing better

ways of treating and new ways of preventing the

condition.

Our researchers are working hard on all aspects of

genetics. Today, we are running 22 research projects

worth around £3million in this field.

Last year, the PDS invested £4.2million in high-quality innovative research. We fund projects in five ways:

• Themed Research – research programmes

that investigate a critical topic for people with

Parkinson’s on which there is little current research

• Project Grants – new projects that tackle specific

problems in Parkinson’s

• Innovation Grants – high-risk, high-reward

projects to open new research avenues in the study

of Parkinson’s

• Prize PhD Studentships – attract outstanding

graduates to the field of Parkinson’s research

• Career Development Awards – encourage

talented researchers to start their own groups to

investigate Parkinson’s


Progress I ��


national developments. Part of my role is to provide information to the Communications side of the team so that they can promote the research we fund and answer queries.

What gets you out of bed in the morning?My father has Parkinson’s so I have a personal interest in working for the Society.

I really like going on site visits and meeting members of the Research Network. Also, I enjoy talking with people with Parkinson’s. Ultimately that’s why we’re here – to help and support people living with the condition.

And finally, what three words describe your life at the PDS?Challenging, rewarding and interesting!

60 seconds with…

Getting to know you

As a child I wanted to be…A member of Enid Blyton’s Famous Five!

If I could go back in time I would…Meet my paternal grandmother – she died the year

before I was born and I’m named after her.

If I went into space I would take…A thick book and my digital camera.

What did you do before you joined the PDS?I was the Research and Development Manager for an NHS trust in East London.

What’s the best thing about working for the PDS?The great people I work with.

What does a Research Grants Manager do?The Research & Development team is split into research operations and research communications. I’m in research operations. I have overall responsibility for the Society’s various grant schemes, making sure they run smoothly and within budget. This means advertising the grants and ensuring that the applications we receive are reviewed.

I also organise the Research Advisory Panel (RAP), which is the committee that decides what research we fund. Professor Paul Bolam, the Chair of RAP, gives a good snapshot of the PDS funding process in his interview on pages 29 and 30.

Another aspect of my job is my involvement with a number of panels, such as DeNDRoN (Dementias and Neurodegenerative Diseases Research Network) – to representing the PDS and keeping us up to date with

Bunia Gorelick Research Grants Manager

For one year now, Bunia Gorelick has been a member of the PDS Research & Development team. We grabbed �0 seconds to quiz her on who she is and what she does.

Bunia in Antarctica

Summer 2008 :Issue 4Issue 4: Summer 2008 Summer 2008 :Issue 4

� � � 4 �

Spotlight on stem cells

New research projects

Themed research

Research equipment shopping list

Site visit

Completed research

Meet... Professor Paul Bolam

60 seconds with... Bunia Gorelick

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Please cut out this form and post it to:

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Summer 2008 :Issue 4

Progress I ��


PDS Research & Development team

Progress is produced by the PDS Research & Development team.

To contact us:

Call 0�0 �9�� 9�� or 0�0 �9�� 8080

Email [email protected]

Visit www.parkinsons.org.uk/research

Write PDS Research & Development team Parkinson’s Disease Society �� Vauxhall Bridge Road London SW�V �EJ

Bunia GorelickResearch Grants Manager

Stacey BuckleyResearch & Development Administrator

Dr Kieran Breen Director of Research & Development

Trish HadfieldResearch Grants Officer (until July 2008)

Dr Lubna ArifResearch Communications Manager

Claire BaleResearch Communications Officer

As little as £5 a month can help us find a cure for Parkinson’sYou can play a major part in the fight against Parkinson’s.

‘The next step’ is a new initiative that enables people to donate directly to research. By agreeing to make monthly or annual gift, you’ll be playing a vital role in making the next breakthrough.

Download a Direct Debit form at www.parkinsons.org.uk/donate or call 01753 688 687 (quoting reference Progress).

Parkinson’s Disease Society of the United Kingdom215 Vauxhall Bridge RoadLondon SW1V 1EJ

Tel: 020 7931 8080 Fax: 020 7233 9908Free Phone Helpline: 0808 800 0303(available Monday–Friday, 9.30am–9pm, Saturday, 9.30am–5.30pm)Email: [email protected] are local PDS branches throughout the UK.Please call 0808 800 0303 for details.www.parkinsons.org.uk

©Parkinson’s Disease Society of the United Kingdom (2008) Charity registered in England and Wales No.258197 and in Scotland No.SCO37554 A company limited by guarantee Registered No. 948776 Registered Office: 215 Vauxhall Bridge Road, London SW1V 1EJ

©Parkinson’s Disease Society of the United Kingdom (2008) Charity registered in England and Wales No.258197 and in Scotland No.SCO37554A company limited by guarantee Registered No. 948776 Registered Office: 215 Vauxhall Bridge Road, London SW1V 1EJ

Avital gift

The PDS Tissue Bank collects brain tissue generously donated by people with and without Parkinson’s. We provide this tissue to researchers around the world who are working hard to find:

• what causes Parkinson’s• a cure and better treatments

Help us continue this essential research and drive towards a cure for Parkinson’s. Register with us today and donate your brain as a vital gift when you die.

Call 020 7594 9732

Email [email protected]

Visit www.parkinsonstissuebank.org.uk

Write PDS Tissue Bank at Imperial College Division of Neuroscience and Mental Health Burlington Danes Building Imperial College London 160 Du Cane Road London W12 0NN

Help us cure Parkinson’s

The Parkinson’s Disease Society (PDS) works with people with Parkinson’s, their carers, families and friends, and health and social care professionals to provide support, information and advice. We are committed to investing in research, education and campaigning to improve the lives of people affected by the condition. The PDS has over 29,000 members, and more than 330 branches, support groups and special interest groups throughout the UK.

How you can help usWe are totally dependent on voluntary donations so if you would like to make a contribution, it will be gratefully received and help us support people affected by Parkinson’s through information, care and research. To make a donation, please call 0�0 �9�� 0�0�To discuss supporting a specific project please call 0�0 �9�� 09 visit www.parkinsons.org.uk/donatewrite to Parkinson’s Disease Society, �� Vauxhall Bridge Road, London SW�V �EJ. Thank you.

Progress magazine: Summer 2008

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Transcript of Progress magazine: Summer 2008