Four decadesof discoveryfinding a cure for Parkinson’s

3Four decades of discovery finding a cure for Parkinson’s

I qualified as a consultant neurologist in the 1950s, a time when the treatment and care available for people with Parkinson’s was incredibly limited. Over the last 50 years, I have seen the services and treatments

improve immeasurably, but we still don’t have a cure for Parkinson’s.

Considerable progress has been made in Parkinson’s research, much of which has arisen through UK research funded by the Parkinson’s Disease Society. We provide great support to the scientific and medical community, which has helped establish the UK as a leader on the world stage.

We need to find a cure for Parkinson’s – a treatment that eliminates all the symptoms of the condition. The Society is dedicated to finding a cure and much of our innovative research shows early signs of promise. We believe that there is hope, but it requires considerable investment. By supporting the Society, you will help us get there.

As a doctor’s daughter, I had always known of Parkinson’s, but it wasn’t until my brother-in-law was diagnosed four years ago that I became aware of the reality of this condition. Parkinson’s involves a daily

struggle to cope with a multitude of disabling and distressing symptoms, and is, as yet, progressive and incurable.

That is why I became involved with the Parkinson’s Disease Society and why I am particularly proud of the work that we do in the field of research. We have supported over £40million worth of pioneering projects which have made a tremendous impact on the treatment and care of people living with Parkinson’s both in the UK and overseas.

In our 40th year, it is heartening to read of the breakthroughs in research described in this publication and of the great strides we have made, but it is also a reminder of how vital it is to continue supporting the Society’s search for a cure if we are to achieve our ultimate goal – a world without Parkinson’s.

Jane AsherPresident, Parkinson’s Disease Society

John Walton FRCP FmedSci(Lord Walton of Detchant) Kt TD MA MD DSc Vice President, Parkinson’s Disease Society

Welcome

4 Four decades of discovery finding a cure for Parkinson’s

Contents

40 years of achievement 5

Unravelling the causes of Parkinson’s 6

More than a movement disorder 8

Changing clinical practice 10

Better drug treatments 12

New hopes for a cure 14

How we fund research 16

Looking forward... 18

5Four decades of discovery finding a cure for Parkinson’s

40 years of achievementThe Parkinson’s Disease Society is the world’s largest membership organisation for people living with Parkinson’s

1 in 8 people is affected by Parkinson’s

You probably know someone with Parkinson’s – the condition affects adults of all ages. For them, everyday activities like walking, talking, eating and sleeping can be extremely difficult. This makes Parkinson’s an isolating and frustrating condition, but the Society can help. In the 40 years since we began, we have supported hundreds of thousands of people with Parkinson’s, as well as their families and friends.

We are the largest non-commercial funder of Parkinson’s research in the UK

£40million on pioneering research

Our research is making a real difference. We have funded pioneering research that has discovered new genes, improved diagnosis and developed better drug treatments. Our research breakthroughs have transformed the treatment and care of people living with Parkinson’s around the world.

We have got further with finding a cure in the last decade than in the last century ... but we still don’t have all the answers

£459 goes towards research every hour

Our cure strategy is working towards the ultimate breakthrough – a treatment that allows people to lead a life free of all symptoms. We are committed to speeding up the delivery of research discoveries to help people with Parkinson’s. We are investing in the most talented researchers at the UK’s best universities and hospitals.

6 Four decades of discovery finding a cure for Parkinson’s

First pieces of the puzzle Parkinson’s occurs when part of the brain – no larger than the end of your thumb – stops making enough of a chemical called dopamine. For some reason, the nerve cells that make dopamine die.

“Understanding Parkinson’s is like doing a 5,000-piece jigsaw puzzle without knowing what the final picture looks like. Researchers have spent the last 40 years laboriously putting together the outer

edges. But the jigsaw is starting to come together and we are beginning to see the bigger picture.”Dr David Dexter, Researcher

Our researchers have made major discoveries about oxidative stress and mitochondria. They have pinpointed them as key players that influence whether nerve cells live or die.

“Over twenty years ago, scientists found that certain nerve cells in the brains of people with Parkinson’s are damaged by oxidative stress. Oxidative stress is a biochemical process – it’s when toxic chemicals build up inside cells, causing them to die.

“Around the same time, our research revealed that the brains of people with Parkinson’s also have problems with tiny energy-producing batteries called mitochondria. Every cell in our body has mitochondria, which make energy to keep cells alive. When the mitochondria stop working properly, the cells get sick and die.”Professor Anthony Schapira, Consultant Neurologist

Unravelling the causes of Parkinson’s

Although we still don’t know exactly why people develop Parkinson’s, research supported by the Parkinson’s Disease Society has fundamentally changed our thinking about the condition. We now know that several different factors in combination can trigger nerve cells in the brain to die. By pinpointing why this happens, researchers can find new and better treatments – moving us closer towards a cure.

Discovering two new genes The study of genes has provided a vital window into understanding Parkinson’s. Scientists have found several genes that are involved in the condition, and two of the most important have been discovered by our researchers.

“I first became interested in the genetics of Parkinson’s about ten years ago. At that time genetics was seen as a non-starter – everyone believed Parkinson’s was entirely caused by

environmental factors. Genetics has now turned out to be incredibly important, and we know that there are both environmental and genetic causes.”Professor Nick Wood, Consultant Neurologist

Less than 5% of people with Parkinson’s have inherited the condition from rare defects in genes. For everyone else,

Parkinson’s is not inherited but caused by a combination of genes that increase the risk, and environmental factors, such as diet and lifestyle.

“In 2004, our research team found the PINK1 gene which leads to a rare form of inherited Parkinson’s. Shortly afterwards we, along with colleagues from the USA, uncovered another gene called LRRK2.

“These genes appear to be important for everyone and keep the nerve cells working smoothly. By understanding how defects in the genes damage nerve cells, we can help all people with Parkinson’s.”Professor Nick Wood, Consultant Neurologist

Researchers around the world are now studying the role of genes, oxidative stress and faulty mitochondria in Parkinson’s. By figuring out what is happening inside nerve cells, researchers can develop new treatments to cure Parkinson’s.

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7Four decades of discovery finding a cure for Parkinson’s

8 Four decades of discovery finding a cure for Parkinson’s

Quality of life matters mostLiving with Parkinson’s affects all aspects of daily life. Although a person’s physical symptoms are treated, their mental health is often overlooked – for example, how a person feels about his or herself and others, or how they are able to deal with life’s demands.

“Our work ignited a crucial debate about quality of life that just wasn’t happening 15 years ago. Specialists typically just considered the physical symptoms of Parkinson’s. They rarely asked how a person felt about living with the condition.

“Our research team designed a questionnaire called the PDQ-39, which rates the quality of life of people with Parkinson’s. It is the first scoring system that asks about mobility, emotions, social support and communication issues. Today, researchers use our questionnaire to monitor quality of life during global clinical trials.”Professor Crispin Jenkinson, Researcher

Mind, mood and bodyAlmost everyone with Parkinson’s will experience other symptoms besides movement problems, such as memory loss, mood changes, bowel problems and difficulties with sleeping. These are called non-motor symptoms. The Society’s Members’ Survey – the UK’s largest ever involving people with Parkinson’s and their carers – found that 92% of people with Parkinson’s have non-motor symptoms.

“Specialists keep track of a person’s symptoms using medical scales. The Unified Parkinson’s Disease Rating Scale is the most widely used scale but it neglects non-motor symptoms.

“We redesigned this scale to incorporate non-motor symptoms. Our new and improved scale is more meaningful to people with Parkinson’s. It gives a complete picture of all the symptoms and will eventually replace the existing scale.”Dr Anette Schrag, Consultant Neurologist

More than a movement disorder Parkinson’s is more than a movement disorder. It affects people in different ways – how you feel, carry out everyday activities and deal with relationships. Research funded by the Parkinson’s Disease Society has revolutionised our understanding of the condition. We have developed three ways of measuring the full range of symptoms, including a person’s physical, emotional and intellectual wellbeing.

Chapter 2

9Four decades of discovery finding a cure for Parkinson’s

Treating non-motor symptomsMany people with Parkinson’s report that non-motor symptoms have a greater effect on their lives than movement problems. However, most of these symptoms can be treated.

“My specialist only asked about my physical symptoms. But I also had dreadful feelings of fear and panic. I was prescribed medication that improved my mobility but the anxiety continued and made my life a struggle. Doing everyday things like going to the supermarket or meeting new people filled me with dread.

“Since my medication has been adjusted, the anxiety has subsided. My confidence has returned and my life has gone back to normal. It is an enormous relief to know that the problem was a part of my Parkinson’s and it is treatable.”Patricia has been living with Parkinson’s for 4 years

“For many years, non-motor symptoms were not considered important and remained untreated. Medical professionals didn’t ask about them and patients didn’t disclose them. So we

developed the Non-motor Symptoms Questionnaire.

“The questionnaire helps specialists around the world recognise and treat non-motor symptoms. Anyone can download the questionnaire from the Society’s website, fill it out and take it to their doctor, consultant or Parkinson’s Disease Nurse Specialist.”Professor Ray Chaudhuri, Consultant Neurologist

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10 Four decades of discovery finding a cure for Parkinson’s

Getting the diagnosis rightParkinson’s is a complex condition with a broad range of symptoms that change over time. No two people are affected in the same way. At present, there is no definitive test for Parkinson’s. Instead, specialists make a diagnosis by examining a person’s symptoms and taking a medical history according to the UK PDS Brain Bank Criteria.

“About one in ten people with symptoms that look like Parkinson’s doesn’t actually have Parkinson’s – they have another condition. The UK PDS Brain Bank Criteria was developed by research supported by the Society over twenty years ago. It is now used by specialists around the world to maximise the accurate diagnosis of Parkinson’s.”Professor Carl Clarke, Consultant Neurologist

Making an accurate diagnosis of Parkinson’s solely from a person’s symptoms is not always possible as it can be mistaken for related conditions. Results from our research have also helped develop modern brain imaging techniques that are used to clarify uncertain diagnoses.

“In the late 1980s, our research team proved that Parkinson’s could be diagnosed by examining people’s brains with a special scanner. We gave people a mildly radioactive form of

the drug levodopa and then scanned their brains. Pictures from the scans showed that nerve cells in the brains of people with Parkinson’s had started to die and did not work properly.”

Professor David Brooks, Consultant Neurologist

Changing clinical practiceOver the past 40 years, research supported by the Parkinson’s Disease Society has transformed the diagnosis and care of people with Parkinson’s. Our research achievements have played a pivotal role in the development of the National Institute for Health and Clinical Excellence (NICE) Guideline for Parkinson’s. This is used by NHS health professionals to give the best care to people with Parkinson’s.

11Four decades of discovery finding a cure for Parkinson’s

A UK-wide network of 250 specialist nursesThe care and treatment of people with Parkinson’s are complicated as everyone’s needs change over time. Our research has shown that support from Parkinson’s Disease Nurse Specialists makes a big difference to people’s ability to cope with the condition. Results from the Society’s Members’ Survey showed that access to specialist nurses is the number one campaign priority. To date, we have invested more than £8million in new roles.

“Our research was pivotal in establishing Parkinson’s Disease Nurse Specialists at the centre of patient care. Specialist nurses are the crucial link between the person with Parkinson’s, their consultant and other healthcare professionals. We showed that people with Parkinson’s who received care from a specialist nurse rated their quality of life as much better.”Sir Brian Jarman, former Head of the Department of Primary Health Care and General Practice

The Society has supported specialist nurses since the first one was appointed over twenty years ago. A combination of our research, campaigning and fundraising activities has resulted in a UK-wide network of around 250 expert nurses. However, if everyone with Parkinson’s in the UK is to have access to a specialist nurse, we need an additional 150 posts. The Society is working hard to achieve a UK-wide network of 400 specialist nurses.

“I am proud to say that I was the UK’s first Parkinson’s Disease Nurse Specialist. Each person with Parkinson’s has very different needs. My role involved making sure my patients and their

families understood the condition, and had the best medicines and support available. By monitoring my patients closely, I helped them cope better with their condition, health and day-to-day life.”Rosemary Maguire, former specialist nurse who received an MBE in 2009 for her services to people with Parkinson’s

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12 Four decades of discovery finding a cure for Parkinson’s

Drugs relieve the symptomsAlthough there’s currently no cure for Parkinson’s, various medicines are available that help relieve the symptoms. Since the 1960s, the most commonly used drug has been levodopa. It can dramatically improve many of the more serious symptoms and help people lead relatively normal lives.

However, as time goes on, some people find that levodopa starts to lose its effect and gives rise to side effects, such as uncontrolled involuntary movements. Some of the distressing symptoms, such as tremors, difficulty with walking and freezing of muscles, may also re-appear but be variable. Within seconds, a person may change from being able to move to being immobile.

Boosting the benefits of levodopa

“About thirty years ago, selegiline emerged as a potential new drug for the treatment of Parkinson’s. Our research tested it in a small group of people with Parkinson’s who were

experiencing problems with levodopa treatment.

“We were one of the first research groups to show that for some people, selegiline made each dose of levodopa last longer. Today, this combined treatment is widely prescribed to control the symptoms of Parkinson’s for longer and minimise the side effects of levodopa.”Professor Andrew Lees, Consultant Neurologist

Better drug treatmentsAlmost everyone who has Parkinson’s will take the drug levodopa at some point. It works very well and can completely control a person’s symptoms for a while. But as Parkinson’s progresses, levodopa can become less effective and cause side effects. Research funded by the Parkinson’s Disease Society has found that taking other drugs alongside levodopa helps it work better for longer. This has benefited hundreds of thousands of people with Parkinson’s around the world.

13Four decades of discovery finding a cure for Parkinson’s

Rapid rescue therapy

“Long before levodopa, researchers found that a drug called apomorphine had anti-Parkinson’s effects. Around twenty years ago a group of people with Parkinson’s who experienced disabling symptoms took part in a new trial, funded by the Society, investigating the potential benefits of apomorphine. The results revealed many of the people taking levodopa with apomorphine showed striking improvements in their symptoms.

“Because apomorphine can be injected, it works more quickly than tablets. This rapid effect means that people have better control over debilitating symptoms for much longer. Apomorphine can also be given directly under the skin. This constant infusion helps to overcome the fluctuations associated with levodopa. To date, apomorphine has already helped many thousands of people manage their disabling symptoms and regain their independence.”Dr Jeremy Playfer, member of the Parkinson’s Disease Society’s Board of Trustees and retired Consultant Geriatrician

“Levodopa worked really well for me for about twenty years. But all that changed a few years ago. My tremor became worse and my whole body would shake uncontrollably. I was finding

it more and more difficult to do simple tasks such as buttoning my shirt or tying my shoelaces. Walking was a struggle. Without warning, my feet would feel glued to the ground. I would be helpless and unable to take another step for minutes.

“My specialist said that the levodopa tablets were no longer controlling my symptoms, so he put me on apomorphine as well. I now have a special pump on a belt around my waist which slowly releases apomorphine into my body 24 hours a day. I have my life back again and can do the things I enjoy, like playing chess and gardening.”Bill has been living with Parkinson’s for 27 years

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14 Four decades of discovery finding a cure for Parkinson’s

Closer to a cureWe need to develop a cure – new cutting edge treatments that will allow people with Parkinson’s to lead a normal life, free of all the symptoms.

“Over the last 20 years, researchers have made major advances in Parkinson’s research. For the first time, we can say that we are closer to a cure than ever before. However, no two people

with Parkinson’s will have the same set of symptoms. There is unlikely to be one cure. Instead there will probably be different cures for different people.”Dr Iracema Leroi, Consultant in Old Age Psychiatry

Transplanting new nerve cellsOne experimental area of research that has shown promise is cell transplantation. The theory is to replace the nerve cells that have died in the brains of people with Parkinson’s with new healthy cells. The Society has been a strong supporter of cell transplantations from the very beginning.

“In the early 1990s, the Society helped fund early cell transplantation trials in a small group of people with Parkinson’s. Human foetal nerve cells were implanted into people’s brains. Although the surgery did not work for most people, two patients showed remarkable improvements.

“Overall, the results were unpredictable and caused disabling side effects in some people. However, researchers are still learning from those initial trials, which have provided the groundwork for further research. Moving forward, the focus for future transplants will be ultimately on stem cells – an area in which the Society invests significantly.”Professor Niall Quinn, Consultant Neurologist

New hopes for a cureToday’s treatments can help relieve most symptoms during the early stages of Parkinson’s – but they do not stop, slow down or reverse the progression of the condition. Research funded by the Parkinson’s Disease Society has pioneered two of the most promising prospects for a cure – cell transplants and gene therapy. Our research is pursuing innovative ways to tackle Parkinson’s that may ultimately lead to a cure.

15Four decades of discovery finding a cure for Parkinson’s

“Sixteen years ago, I was fortunate to have taken part in the Society’s clinical trial for cell transplants. I had two separate operations, one on either side of my brain, and I started to feel better

three months later. I feel incredibly lucky: the cell transplants have given back my independence. I still have minor symptoms but I’ve been able to stop taking most of my medication and continue activities like driving.

“Despite the risk and uncertainty, this experimental treatment has helped me. Others, however, have not been so fortunate. More research is needed to make cell transplants safer and work better.”Chris has been living with Parkinson’s for 25 years

Adding new genesAnother dynamic area of research where groundbreaking treatments are being developed is gene therapy. This involves adding new genes to nerve cells in the brain to make them work better.

“Gene therapy emerged as a new concept in the late 1980s and the Society was at the forefront of this research. Our research found new ways of successfully putting genes into cells. Adding certain genes into the brains of people with Parkinson’s has the potential to rescue dying nerve cells or help nerve cells make more dopamine.

“Research funded by the Society showed that gene therapy relieved symptoms in animals with Parkinson’s-like symptoms. Today, there are several gene therapy treatments in development and being tested in people with Parkinson’s.”Professor David Latchman, Researcher

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16 Four decades of discovery finding a cure for Parkinson’s

How we fund research

Research finishes and the results are reported in scientific journals, conferences and the Society’s research publications.5

We invite applications for our research grants from scientists, clinicians and healthcare professionals. Each application includes:

a detailed project plan

a clear explanation of the benefit to people with Parkinson’s

a justification of resources required (money, time and people)

1

Every application is strictly evaluated by:

at least four independent experts from around the world

our Research Advisory Panel

people affected by Parkinson’s

2

New projects are approved and research starts.3

Each project is closely monitored through visits and annual assessments.4

17Four decades of discovery finding a cure for Parkinson’s

“As a member of the Association of Medical Research Charities (AMRC), the Parkinson’s Disease Society has signed up to very high standards that ensure accountability and

transparency in the way it gives out its money.

“The Society is a role model for how other charities should be working. Those who donate to research into Parkinson’s can be assured that they are funding high quality research.”Simon Denegri, CEO of the AMRC, a membership organisation of the leading medical and health research charities in the UK

“Our Research Advisory Panel is made up of 32 leading scientists, neurologists and healthcare professionals who are international experts in their specialist areas of research.

“In every decision, we also involve six people affected by Parkinson’s from the Society’s Research Network. This ensures the projects we recommend are scientifically excellent and relevant to people with the condition.”Professor Paul Bolam, Chair of the Parkinson’s Disease Society’s Research Advisory Panel and Researcher

“As a person with Parkinson’s, I know how crucial it is that a cure is found. By working with the Society, I use my passion and commitment to help make this shared hope a

reality. We must keep raising more money to fund more research to make this happen.”Dr Shirley Ratcliffe has been living with Parkinson’s for 10 years. Shirley is a member of the Parkinson’s Disease Society’s Board of Trustees and Special Parkinson’s Research Interest Group

Our cure strategy

Over the last 40 years, the Parkinson’s Disease Society has invested more than £40million in the highest quality research. Now, to mark our 40th year, we are focusing

more strongly than ever on finding a breakthrough to a cure. Building on existing discoveries and exploring innovative areas of research, we are continuing to support the UK’s most talented researchers and to work closely with the world’s experts in Parkinson’s.

We have set ourselves an ambitious challenge: one that offers great promise but requires significant investment. Be part of our challenge, support research and help to find the ultimate breakthrough – a cure.

Dr Kieran Breen Director of Research & Development

18 Four decades of discovery finding a cure for Parkinson’s

Invest in a cure

The Parkinson’s Disease Society is proud of the great accomplishments that have come from our research. We are

the UK’s largest non-commercial funder of Parkinson’s research, and I’m really encouraged to see how our achievements have benefited the treatment and care of so many people with Parkinson’s.

Looking forward...

The time is now to build momentum and focus even more on finding a cure for Parkinson’s. Join us in our breakthrough journey – invest in our exciting research and contribute to a cure for Parkinson’s.

Steve FordChief Executive, Parkinson’s Disease Society

I would like to thank the many individual donors, trusts and other grant making organisations who are making this possible, as well as everyone who fundraises tirelessly and all those who have left us gifts in their Wills. We are completely dependent on voluntary contributions, so without your valuable support we would not have taken such huge steps forward in research.

“As a carer, I’ve a constant sense of frustration that there is so little I can do about my husband’s condition. Playing a part in shaping the Society’s research programme helps channel my frustration and

enables me to do something positive and proactive.”Belinda whose husband has been living with Parkinson’s for 7 years. Belinda is a member of the Parkinson’s Disease Society’s Research Network

“Everyone affected by Parkinson’s should become a member of the Society and get involved in research – it’s the only way of getting rid of this dreadful disease.”Surinder has been living with Parkinson’s for 10 years

“Life goes on ... but the Society’s research gives great hope to people with Parkinson that a cure will be discovered and medication improved.”Mike has been living with

Parkinson’s for 5 years

“I am optimistic. Over the last decade the Society’s research has made great strides towards finding a cure… It’s just a matter of time people have the will and science is moving in the right direction.”Dennis has been living with Parkinson’s for 3 years

© Parkinson’s Disease Society of the United Kingdom. 215 Vauxhall Bridge Road, London SW1V 1EJ Charity registered in England and Wales No. 258197 and in Scotland No. SC037554. A company limited by guarantee. Registered No. 948776 (London)

“The time is now to build momentum and focus even more on finding a cure for Parkinson’s. Join us in our breakthrough journey – invest in our exciting research and contribute to a cure for Parkinson’s.”Steve FordChief Executive, Parkinson’s Disease Society

Get involvedFor more information about the Parkinson’s Disease SocietyCall: 020 7931 8080Email: enquiries@parkinsons.org.uk Visit: www.parkinsons.org.uk

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