National Amyloidosis Centre News

Introduction ISSUE 2: October 2013

The first half of 2013 has been a busy and productive period at the National Amyloidosis Centre. The number of patients referred to us has continued to increase steadily by about 15% per year.

In February the NAC hosted 130 participants from all around the UK at the Fifth Annual UK Amyloidosis Network (UKAN) meeting. The UKAN, a national network of clinicians and researchers with an interest in amyloidosis, has grown exponentially since it was conceived by Dr Ashu Wechalekar and founded by the NAC consultants in 2009 as a yearly forum for promoting earlier diagnosis and clinical and research excellence in amyloidosis. Back in 2009 most participants in UKAN meetings were haematologists, but the 2013 meeting also included many cardiologists and nephrologists, reflecting the growing recognition of the importance of a multidisciplinary approach to amyloidosis. There were lectures by NAC consultants and research fellows and by eminent guest lecturers from Spain and the US. Patient representatives from the newly formed UK Amyloidosis Advisory Group (UKAAG) also attended. A new patient information website at http://www.amyloidosis.org.uk/ has been launched under the auspices of UKAAG.

The doctors at the NAC authored and co-authored several recently published papers on a new magnetic resonance (MR) technique called “equilibrium contrast-enhanced imaging.” This technique holds promise for improved monitoring of amyloidosis in the heart. Other recent publications by the NAC consultants have included a state of the art update on AL amyloidosis for treating physicians, a review of the literature on hereditary fibrinogen amyloidosis and co-authorship of a European collaborative study of treatment outcomes in patients with late stage cardiac AL amyloidosis. This is the largest study of its type, as these patients had previously been poorly studied.

IN THIS ISSUE

Introduction 1

Patient stories: The Nicholas twins 2

Hereditary amyloidosis fact-file 4

More on hereditary amyloidosis 5

Patient & carer story: Martin and Cheryl Bolton-Smith 6

Fundraising 8

A letter of thanks from Professor Sir Mark Pepys 9

Donations 10

National Amyloidosis Centre, UCL Division of Medicine, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK www.ucl.ac.uk/medicine/amyloidosis

Professor Philip Hawkins FMedSci, Director of the NAC, speaking at the 5th Annual UK Amyloidosis Network meeting at the Royal Free Hospital, London.

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Patient stories: Vincent and Keith Nicholas

Our mother passed way from familial amyloid polyneuropathy (FAP) in 1991 at the age of 66.

In 1989, after she had suffered four years of invasive procedures and misdiagnoses, doctors suggested that she may have amyloidosis. Soon after this, our father mentioned her illness to a man he met in a local shop. On hearing that this man was a doctor, our father asked in desperation if he knew of anyone who specialised in amyloidosis and amazingly he did. The following week my father had a phone call from the Hammersmith Hospital inviting my mother and him to attend a consultation with Professor Mark Pepys and Dr Philip Hawkins. Tests showed that she had familial amyloid polyneuropathy (FAP) but unfortunately her condition was too advanced for her to undergo a liver transplant.

After she was diagnosed, we realised that other relatives had probably also died from this condition. Since then FAP has been diagnosed in several of our uncles, aunts and cousins.

Vincent’s story:

I and my identical twin brother, Keith, were only 30 years old when our mother was diagnosed. After talks with Dr Hawkins we felt that we would like to help the doctors with their research and decided to see if we had the gene. We were informed that we would need to be mentally and emotionally ready to receive the news/diagnosis. When we were 35 years old, we decided to go ahead and after a routine blood test. Dr Hawkins told us that we had both inherited the mutation that causes FAP. My wife and I wrote a ‘bucket list’ as we didn’t know how long I had to live. My twin brother Keith felt that the knowledge that he had FAP did not affect how he lived. He put the problem to the back of his mind as he believed he did not need to worry until the day the symptoms would present themselves.

Even though we had no symptoms we were monitored on an annual basis by the National Amyloidosis Centre which was then at the Hammersmith Hospital. This way they would be able to use us in their research and see

how we progressed. We went through extensive blood and nerve tests and scans - sometimes twice a year. Later we had heart and rectal biopsies.

My symptoms started when I was 50 years old. I can pin point the exact date as I noticed pins and needles in my hands and feet at my youngest daughter’s birthday party on 6th October 2009. I went to get some shopping and ran from the car quickly and after 10 metres I started to feel dizzy and had to sit on the floor quickly. Around this

time I began to go off some foods and had diarrhoea. I felt dizzy when climbing stairs and lost feeling in my feet and legs. I had to have a pacemaker with a defibrillator fitted to regulate my heart rate.

Keith had similar symptoms to me, and we discussed the situation with Professor Hawkins and the amyloidosis team. It was established that the only possible option would be to have a liver transplant. There was no proof that this would work – so we were between a rock and a hard place when being faced with our decision. What else could we do except go for it!

Once a matching liver became available I had the transplant. This was in February 2010. Keith

had his transplant six months later.

I initially took six medications per day including diflunisal, midodrine, anti-rejection drugs and warfarin. I spent 3 months in hospital and had blood tests every day – sometimes twice a day. This was the worst thing for me! On returning home I suffered some collapses due to low blood pressure and weight loss and had to be re-admitted to hospital. Following the liver transplant I was more outspoken. This has remained although softened somewhat. I continue to look at life in a more black and white way although procrastination can be a problem!

The side effects of the drugs, liver transplant and the amyloidosis have included low blood pressure - especially when walking up stairs and slopes/hills; poor circulation in the feet, legs and hands which can make it

Vincent and Keith celebrating the first year anniversary after their liver transplants

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difficult to walk; loss of sensation in my extremities; loss of sexual function and interest in anything of a sexual nature/sex drive; loss of physical strength and stamina; difficulties with vision in bright sunlight; I can only drink certain coffees and eat certain foods as my body rejects others quite vehemently! I have had to accept that the number of tasks that I can manage on a daily basis has had to be reduced – both at home and at work. My whole lifestyle has had to be re-evaluated and my family have also had to adjust. My wife has had to rise to the challenge of taking on many more manual tasks that I would have previously been able to manage – moving heavy furniture, heavy gardening jobs, etc.

I have returned to work on a full time basis with my job description being altered to adjust to my strengths. I only need to take four tablets a day now. I try to swim every so often and I have foot and leg massages which give my feet more feeling and lessen some of the pins and needles. Some days I have more energy than others. I can fall asleep almost anywhere when I am really tired. This is not always appreciated when my wife is required to go out to work, look after me, our home and our two daughters – 9 and 11 years of age! I find it difficult to walk very far or to cycle at a fast enough speed for my children. It all seems to take a lot of effort. My family and I are happy that I am still here though!!

As I was the first in the family to go through the liver transplant I have been able to support other family members – my twin and cousin. Keith and I discussed who would ‘go first’. I decided to go first even thought I am the youngest twin – by 45 minutes! We now have other cousins who are on the waiting list around the world, who we have been in close contact with.

Keith’s story:

Like Vincent I started to experience pins and needles in my hands and feet, stomach problems and fatigue when I was 50 years old. I had the amyloidosis symptoms for six months longer than Vincent, so my weight had already decreased and neuropathy bowel problems were so severe that there was a chance that I would not be well enough for a liver transplant which was my only hope of survival. This was a very, very emotional time. I felt that my life was over as I didn’t want to go through what my mother, uncle and aunt had suffered. I had watched them all die a slow and very cruel death. But my family and friends helped me through and pushed for the transplant.

I had my pacemaker fitted and waited. Once a liver match had been found it was decided that the transplant could take place. Phew! I knew what I was getting into

as I had seen what Vincent had been through and after all, I had said that I was happy for him to go first!

As for the drugs, because Vincent had been through it first they had a better idea of which drugs and doses I should take. They knew I may fall over/collapse so were ready for this. That day did arrive – and I was at home! Luckily a friend was there to pick me up and phone Vincent. We only live about 30 minutes away from each other. They took me to London, to the Royal Free Hospital where I stayed for 8 weeks. Because of my low blood pressure and muscle wastage I had to learn to walk upright again, first with a Zimmer frame and then a walking stick, small steps at a time. I would never have achieved this if not for the persistent help from a wonderful but forceful doctor friend. I took midodrine for low blood pressure, which made my head itch.

Eight months after the liver transplant I returned to work full time. It is understood that sometimes I need to work from home and I take it easy on occasions, otherwise I get very fatigued. Like Vincent I have had to adapt my lifestyle to accommodate the amyloidosis symptoms and their effects. I occasionally swim and go to the gym – trying to build up my muscles and stamina. My friends and family are very understanding. Like Vincent, my outlook on life has changed in that life is too short to worry about the mundane things.

Familial amyloid polyneuropathy (FAP)

FAP is the most common form of hereditary systemic amyloidosis. In people with FAP, a blood protein called transthyretin (TTR) is the amyloid precursor protein that forms amyloid deposits. FAP is one of three distinct, different types of ATTR amyloidosis.

TTR is a normal blood protein present in everybody. Most TTR in the body is made in the liver. People who are born with inherited mutations in the TTR gene produce abnormal “variant” TTR throughout their lives. The “variant” TTR is amyloidogenic (amyloid forming). Over the course of several decades, people like Vincent and Keith with inherited TTR gene mutations may develop symptoms of disease caused by the build-up of amyloid deposits.

Liver transplantation is a treatment option for some people with FAP. The liver which makes the “variant” TTR is removed and replaced by a donor liver making normal, “wild-type” TTR. The aim is to prevent the formation of further amyloid deposits by reducing the supply of the amyloid forming precursor “variant” TTR.

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Our message to amyloidosis sufferers, especially those with FAP:

There is now more hope for those diagnosed with amyloidosis as new drugs are being developed that will treat this without – hopefully – having to go through a liver transplant. Early symptoms of FAP need to be recognized so that, if appropriate, patients can be placed on the transplant list as soon as possible.

It is important to seek out a good counsellor and to have a good support network – whether this is family or friends. Ours have been and continue to be wonderful. You really need them! An understanding boss is essential – which amazingly we both have. We witnessed patients on our wards who did not have supportive employers with the result that they lost their jobs, then their homes – because they could not meet their mortgage payments – and on one occasion the marriage broke down completely. It is also important that you need to accept your limitations. It has taken us a long time to adjust to this!

Have faith in the amyloidosis and liver transplant teams as they really know what they’re doing. Inform them of anything that you are worrying about regarding your health – then they can help. If you don’t tell them – they can’t. Be aware that the initial tests can be onerous – electric shock tests, hands in iced water etc.!!!

It is important to remember that the time waiting on the liver transplant list can be very emotionally draining – feeling on tenterhooks every time the phone rings! Is it time?! Also feeling that you may not be coming back from the operation whilst driving to the hospital and how important it is to get your house in order as soon as you have the diagnosis.

Thanks need to go out to all our families and friends, without them we would not be where we are today (three years on). This journey has brought us all much closer. They have taken days off work to drive us up to London in the early days after the liver transplant as we live about 2 hours away; they have picked us up off the floor when we have collapsed; they have brought us food; cared for us – even the really personal stuff; gone through hell and high water emotionally whilst waiting for us to come out of theatre. Our bosses and work colleagues have been equally amazing – bearing with us when we didn’t feel up to much, when we collapsed after walking up the stairs as well as taking us to the station to get us home, lift sharing, carrying our bags and lending a helping hand when needed. We also want to thank the wonderful teams of professionals that have carried us through this experience, as well as Vincent’s GP surgery who have funded his medication. Without all of these individuals we would probably not be here today. A scary thought!

Hereditary amyloidosis fact-file AL amyloidosis, AA amyloidosis and ATTR senile systemic amyloidosis are not inherited conditions. What causes hereditary amyloidosis? Hereditary amyloidosis is caused by inheritance of an abnormal copy of a gene, known as a mutation. These mutations lead to lifelong production of an abnormal, amyloid forming (“variant”) form of a normal protein. The Table on the next page lists the different types of gene mutation that can lead to formation of a “variant” protein that can be amyloidogenic.

When do symptoms usually start? People with mutations causing hereditary amyloidosis produce an abnormal, amyloidogenic “variant” protein throughout their lives. Over the course of several decades, usually by the time these people are middle-aged or older, they may develop symptoms of amyloidosis. Different types of hereditary amyloidosis can cause a wide variety of different symptoms, affecting different parts of the body, and appearing at different ages. Disease manifestations may differ quite considerably between different families with the same type of hereditary amyloidosis and even between individuals from the same family.

What are the chances of children being affected? Inheritance of hereditary systemic amyloidosis syndromes is “autosomal dominant.” This means that the presence of just one copy of a mutated gene, passed down from one parent, can cause the disease. Each child born to a parent with hereditary amyloidosis has a 50% chance of inheriting the mutated gene. However, not all people who inherit one of these mutations will actually develop clinical problems. Some people with a mutation develop only a small and insignificant amount of amyloid in their body and others seem to accumulate none at all. This is called incomplete penetrance.

But there are a number of different types of hereditary (inherited) amyloidosis, as shown in the Table on the next page. These conditions are rare, affecting around 12% of the patients seen at the NAC. Some otherwise rare forms of hereditary amyloidosis are common in local regions of Portugal, Sweden and Japan where the descendants of a ‘founder’ patient or patients have lived for many generations. In recent years the diagnosis has been made more frequently than it was in the past, as diagnostic techniques and understanding of genetics have progressed. Research into these rare diseases has greatly helped to shed light on the commoner types of amyloidosis.

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Different types of hereditary amyloidosis (in order from most to least common)

Name of hereditary amyloidosis syndrome

Name of the gene which contains a

mutation

Name of amyloid type Symptoms

Familial amyloid polyneuropathy (FAP)

TTR (transthyretin) gene ATTR amyloid • Neuropathy (nerve disease) • Heart disease • Carpal tunnel syndrome • May be eye, kidney and spleen

disease

Hereditary amyloid cardiomyopathy

TTR (transthyretin) gene ATTR amyloid • Heart disease • Carpal tunnel syndrome

Hereditary fibrinogen A α-chain amyloidosis

Fibrinogen A α-chain gene

AFib amyloid • Kidney disease

Hereditary apolipoprotein AI amyloidosis

Apolipoprotein AI gene AApoAI amyloid

• Kidney disease • High blood pressure • May be heart, liver, spleen

disease

Hereditary apolipoprotein AII amyloidosis

Apolipoprotein AII gene AApoAII amyloid

• Kidney disease • High blood pressure • May be heart, liver and spleen

disease

Hereditary gelsolin amyloidosis Gelsolin gene AGel amyloid • Eye disease • Skin disease • Cranial nerve disease

Hereditary lysozyme amyloidosis Lysozyme gene ALys amyloid • Kidney disease • Liver disease • Stomach disease (rare)

Hereditary β2-microglobulin amyloidosis

β2-microglobulin gene Aβ2m amyloid • Bowel disease

Rare hereditary amyloidosis may help unlock amyloidosis mysteries

All patients with amyloidosis may eventually benefit from recent discovery of an extremely rare type of hereditary amyloidosis, in which the amyloid deposits consist of a “variant” form of a protein called β2 (pronounced “beta-2”) microglobulin, or β2m. Study of this newly discovered variant protein may help to provide fresh insights into a number of fundamental unanswered questions about amyloidosis. Why do amyloid deposits form when and where they do? Why do different patients with same type of amyloid develop amyloid in

different organs? How can we prevent amyloid deposits from forming and how could we remove them?

Four members of a single French family were diagnosed with amyloidosis affecting the gut, spleen and autonomic nerves. Doctors only diagnosed hereditary amyloidosis after some of the four had been ill for up to 20 years. After tests for the known types of hereditary amyloidosis came back negative, researchers employed a new, state of the art technique called “proteomics”, which showed

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that the French patients all had a type of hereditary amyloidosis that had never been described before, with amyloid deposits made of β2m. Genetic tests confirmed that all four affected patients had a single, previously unknown, mutation in the gene for this protein.

However it has long been known that normal β2m can form amyloid because patients with kidney failure who were treated for years by dialysis often developed β2m amyloid deposits. This resulted from high concentrations of β2m in the blood because this protein was not efficiently cleared by dialysis procedures. Dialysis related β2m amyloidosis has become less common since new dialysis procedures have improved the clearance of β2m but it remains a significant problem. Professor Vittorio Bellotti at the UCL Wolfson Drug Discovery Unit in the Centre for Amyloidosis and Acute Phase Proteins, has studied β2m as a model of amyloid fibrillogenesis (fibril formation) for many years and led the remarkable new studies of the variant β2M.

In dialysis related β2m amyloidosis, amyloid deposits are mainly in the bones and joints and consist of normal β2m, not variant β2m. This condition is not inherited. Neither β2m amyloid affecting the gut, spleen and nerves, nor hereditary β2m amyloidosis, had ever been seen before. Hereditary systemic amyloidosis due to a mutation in the β2m gene is a very different condition from dialysis related β2m amyloidosis.

Further research showed that the variant β2m produced by the mutation present in the French patients is the most amyloidogenic protein ever seen. It forms amyloid deposits very readily and swiftly in the laboratory and provides an ideal, unique opportunity for detailed study of the process whereby amyloid deposits form. The newly discovered mutated β2m will help Bellotti and his team to unravel some of the mysteries about how, where and why amyloid deposits form. It will also be very useful for testing experimental drugs aimed at preventing formation of amyloid deposits and removing existing deposits.

“When the going gets tough, the tough get going”

Cheryl and Martin Bolton-Smiths’ story

Cheryl's early experience of amyloidosis began in 2008 at the age of 50 and follows the pattern of many patients. It took until 2011 to arrive at a correct diagnosis. During that time, in addition to losing a much loved father, Cheryl suffered symptoms with which many sufferers will be familiar: extreme tiredness, severe weight loss, low blood pressure, loss of appetite, altered taste, abnormal and frequent stomach cramps and diarrhoea. During this time Cheryl had a hysterectomy, had helicobacter infection twice and on occasions collapsed and had to be hospitalised. Despite numerous tests, doctors struggled to find a reason for her symptoms. Irritable bowel syndrome, depression, stress and recovery from the surgery were all suggested as possible culprits. Cheryl had been a very active dancer but had to abandon her passion soon after her illness took hold. Throughout the summer of 2009 Martin, a London taxi cab driver, had to give up work to care for her. With Cheryl's debilitating and often life threatening symptoms, there had to be something seriously wrong and Martin had to plead with the local doctors to investigate Cheryl's condition

further. Cheryl was tested for several serious diseases including cancer but the tests proved inconclusive. She had endless consultations, some of them private. Martin considered selling assets such as their home and his taxi cab, which was his source of income, if it meant Cheryl would get better.

Cheryl was admitted to St George's Hospital, Tooting, in March 2011 where she remained for 9 weeks. She was given several drugs to help with the diarrhoea and low blood pressure and doctors suggested that she may be suffering from some sort of rare blood or bone marrow cancer. Martin was very anxious when Cheryl was discharged as to how he was going to cope looking after her at home when she was so very ill. He was also concerned that no definitive diagnosis had been given and asked the neurologist treating Cheryl at St George's if her case could be reviewed by someone more senior.

In May 2011, urine and bone marrow tests suggested amyloidosis and Cheryl was eventually referred to The National Amyloidosis Centre where diagnostic testing

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confirmed she had systemic AL amyloidosis. Martin promptly did some research but found the information difficult to understand. It was a frightening moment to hear that Cheryl had a rare, complex and incurable disease which neither she nor Martin had ever heard of. However, after three years of misdiagnoses it was also a relief to know the correct diagnosis at last. Now that Cheryl was in the hands of the expert doctors at the NAC, appropriate treatment could start.

Cheryl was very weak but being a fighter like her Dad, she was determined to be positive despite suffering from the amyloidosis symptoms and side effects from her initial treatment with melphalan and dexamethasone.

By 2012 Cheryl had completed her cycles of melphalan and dexamethasone and was started on revlimid, a less aggressive oral chemotherapy drug. Her extreme tiredness continues and it is never possible to know what each day will bring as the symptoms of AL amyloidosis are not predictable. On her better days Cheryl likes to do what she can around the house and especially enjoys baking. She is determined that the disease will not beat her. Her cheerful, kind nature and caring attitude towards others are an inspiration to all and help Martin and her sister Jessie through the dark times of wondering what the future holds. Cheryl’s recent scan showed that amyloid deposition had not increased but the hoped for regression had not taken place. Now she is about to start another chemotherapy regime.

Soon after Cheryl’s diagnosis, Martin decided that he would do something positive towards helping research

into the disease and so far has organised or participated in 5 events and raised over £15,000 for UCL’s Amyloidosis Research Fund. He also feels it is crucial to raise public awareness of the disease so his ventures have a twofold aim. He cannot help regretting that by the time Cheryl was diagnosed, her disease was advanced and more difficult to treat. In Horsham, where he and Cheryl live, Martin has come to be known as “The Fundraiser Man” and has demonstrated a powerful determination to raise money for the UCL Amyloidosis Research Fund until a treatment is found that will improve the quality of life for sufferers. Martin has set himself tough sporting challenges taking up marathon running at the age of 53. His latest achievement was completion of the Brighton Marathon on April 14th 2013.

Martin sometimes feels overwhelmed and wonders how he can keep going with his training, working full time, family pressures and caring for Cheryl. He only has to remind himself of Cheryl’s suffering and his loving commitment never falters. His own interests have had to take a back seat but this is not important to him as amyloidosis has robbed Cheryl of living the life she loved. Martin’s advice to anyone finding themselves in a similar position is to never give up hope, to fight this terrible disease with all your emotional and physical strength and put your faith in the wonderful doctors at the NAC. Turning positives into negatives is Martin’s way. He asks all sufferers and carers to give generously to fundraising efforts that will ultimately benefit them too. This will gladden his heart and, he hopes, hasten the day that an anti-amyloid drug will become available to all.

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Fundraising £16,500 raised for The UCL Amyloidosis Research Fund

By Pat Pinchin

Since December 2011, Martin Bolton-Smith has raised over £16,500 for the UCL Amyloidosis Research Fund. Here are the events he has organised. He hopes they will inspire others to take up the challenge and organise a charity fund-raising event for the NAC:

• Bowls challenge at a Horsham bowling club – December 2011 • Golf day – tournament between local clubs with Martin also setting himself a personal challenge of

completing the 18 holes within a time limit – March 2012 • Flog It at a local pub – April 2012 • Cabbies’ collection 2012 and 2013 – Martin is a London cabbie and he spent 2 days at Heathrow airport

collecting for amyloidosis with donations from his work-mates • Barnes Green Half Marathon – Sepember 2012 • Brighton Marathon – April 2013

On Thursday, April 4th, Martin Bolton-Smith was presented with a cheque for the money he had raised by his participation in the Barnes Green half marathon. The presentation ceremony was held in Guildford by the Surrey Freemasons, who had allowed Martin to use their “my donate” affiliation for his fundraising. After receiving the cheque, there was a surprise accolade in store for Martin. As none of the 5 senior members of the small NAC medical team were able to attend, Professor Sir Mark Pepys, who established the National Amyloidosis Centre and the UCL Centre for Amyloidosis and Acute Phase Proteins, and is now Director of the UCL Wolfson Drug Discovery Unit, had written a very warm letter in which he expressed his personal appreciation of Martin’s charity work and the generosity of his donors. The full letter appears on the next page.

Martin’s speech and Sir Mark’s moving words made such an impression on the audience that more donors for Martin’s next appeal (the Brighton Marathon on April 14th), promptly came forward.

True to form Martin is already thinking about his next challenge and fundraising event for the Amyloidosis Research Fund. If you would like to contact Martin for ideas of how to set about organising your own charity event for amyloidosis, please contact him: m.boltonsmith@ssesurf.co.uk.

London to Paris for Amyloidosis!! By Jo Jerden

On 26th September 2013 four of my colleagues (and one of their partners) undertook the gruelling (but scenic) ride from London to Paris in aid of raising further funding towards amyloidosis research, and more specifically the Cover Slipper Fund. Nick Jones, Tim Godden, Paul Brown and Simon Greenhalgh traded in their desks for four days and 279 miles of pedalling. The Cover Slipper Fund was set up following my diagnosis of amyloidosis in 2012. Our specific aim is to provide the Centre with funds towards a much needed piece of equipment called a Coverslipper Machine which will help the histologists to prepare both clinical and research slides. With the help of relatives, friends and colleagues undertaking mountain climbing challenges, hosting tea parties and the likes, we have so far raised £12,000 of the £23,000 target. I am totally in awe of the challenge these guys undertook - I know for sure my bottom would be too saddle sore to endure this for more than an afternoon!

It would be great if you could show your support for the team by visiting http://www.justgiving.com/Joanna-Jerden-CoverSlipperFund. More details of the Fund can also been seen on this site.

National Amyloidosis Centre News Issue 2: October 2013 9

A letter of thanks From Professor Sir Mark Pepys

Dear Martin

It is a great pleasure and a privilege for me to thank you, once again, for your absolutely magnificent fund raising efforts on behalf of the UCL Amyloidosis Research Fund which supports the Centre for Amyloidosis and Acute Phase Proteins and its UK NHS National Amyloidosis Centre. The wonderful sum you have now raised derives from the immense generosity of many donors and we are very grateful to everybody concerned. Amyloidosis is a relatively rare and very unpleasant condition which damages the health and shortens the life of almost all individuals who have it. We and our colleagues in this field around the world have made, and are making, substantial progress but much remains to be done.

I started to work on amyloidosis in 1976 and nearly 40 years on knowledge of the disease, its diagnosis, its treatments and its outcome have all improved dramatically. My group and I have contributed some of the key innovations and developments and, since 1999 we have had invaluable support from the charitable donations to the Amyloidosis Research Fund.

From 1979 all my work was funded by the Medical Research Council, which distributes government, that is the tax payers’, money for medical research. By 1990’s we had become the de facto national referral centre for amyloidosis and when we moved from Hammersmith Hospital to UCL and the Royal Free Hospital in 1999, the Department of Health had created a scheme for direct funding of highly specialised NHS services. I applied successfully for establishment and funding of the National Amyloidosis Centre and appointed my colleague, Professor Philip Hawkins, who had trained and then worked with me since 1986, to be its Clinical Director. At that time we were seeing about 300 patients per year. Now he and a total of about 50 staff in the National Amyloidosis Centre see more than 3,000 patients per year and that number comprises a doubling in the past 5 years. So far this massive increase, enabling us to deliver the world’s best diagnosis and management advice for amyloidosis, has been generously funded by the Department of Health and also supported by the Royal Free NHS Trust and the Royal Free Charity. Unfortunately, the future with the new NHS reorganisation is very unclear and uncertain.

In parallel with the tremendous development and progress in clinical service delivery for patients, I have been focussing on design and development of new approaches to treatment of amyloidosis, especially measures to remove amyloid deposits from the tissues and organs where they are causing damage and thus disease. To pursue this goal, I retired in 2011 as Head of the Division of Medicine at the Royal Free Campus of UCL and became Director of the UCL Wolfson Drug Discovery Unit, which I set up for this purpose. Sadly, drug development, that is the invention of new medicines and all the work needed to make them available for patients, is generally agreed to be the slowest, most difficult and most expensive undertaking conducted by the human race! It is quicker and easier to send a man to the moon! Nevertheless we are making progress. GlaxoSmithKline, one of

the world’s largest and best pharmaceutical companies, has licensed some of my patented inventions of new potential medicines and we have been developing them together for the past 4 years. Finally in April this year, GSK will start clinical testing in amyloidosis patients of the most developed of my new treatments. If the new treatment is safe, we may know within the following year whether it is also effective and whether it is sufficiently promising to justify the hundreds of millions of pounds which will then have to be spent to make it into a real medicine, available for amyloidosis patients generally. Other developments, both in the Wolfson Drug Discovery Unit and in laboratories and companies around the world, also promise much hope for the future.

The very long, slow and costly processes of research and development are almost entirely funded by government, that is tax payers, by medical charities and by industry. But in all cases, obtaining the funding is also slow and it is invariably rigidly awarded for particular tasks. Also our relationship with GSK requires us to provide the expertise and facilities which are our strength, and these are not funded by the company; revenue will flow to our institutions only if and when we have a successful medicine. This is incompatible with the highly speculative nature of original discovery research when you never know what results will emerge, what new methods, techniques, equipment or personnel and skills may be needed to solve problems and make progress. Here the Amyloidosis Research Fund plays an invaluable role by enabling us to move swiftly to seize whatever opportunities arise, whether it is to purchase an essential piece of equipment or a special chemical or other reagents for experiments, or to obtain specialist expertise or services, or employ a new person to do a specific and necessary job in the laboratory or the clinic.

I cannot overemphasise the importance of having this priceless flexibility. It has contributed on a daily basis to all the progress we have made, which is reflected by our many high impact publications, our new inventions and patents, our uniquely strong relationships with GSK, representing the pharmaceutical industry without which there would be no drugs, our many high value research grants from the MRC, the Wellcome Trust and other bodies, and, of course, our entirely NHS funded clinical service which exists to care for the patients who are at the heart of everything we do. Every single person who has donated to the Fund and every individual who has helped to stimulate and organise these donations should be very proud of what they have done.

I am extremely sorry that I am abroad at this time and thus not able to be present in person to thank you and to explain further the great significance of what you have done and are doing. I earnestly hope that I shall have the opportunity to do so in the future.

With kindest regards and all best wishes Professor Sir Mark Pepys Director, Wolfson Drug Discovery Unit

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Donations To ensure that your donations go directly and exclusively to the NAC, please send directly to us or contact Beth Jones on 020 7433 2802 or beth.jones@ucl.ac.uk. Donations to the fundraising activities mentioned on page 8 will also come directly to NAC.

All university based medical research depends on funds that are fought for in open competition (grants) from the Government-funded Medical Research Council and other charitable bodies. Their renewal depends on a successful research programme and the NAC has an excellent track record in this respect. However, there are constant shortfalls and every penny from other sources is received with sincere gratitude, and is used specifically and in its entirety for amyloidosis research. You can make an online donation at:

http://www.ucl.ac.uk/medicine/amyloidosis/research_fund

or make a donation by post. A gift aid form is included here and is also available online or from:

Beth Jones National Amyloidosis Centre Division of Medicine, Royal Free Campus University College London Rowland Hill Street London NW3 2PF UK

UCL Medical School is part of University College London (UCL) which is a registered charity. Due to changes in the Budget nearly all gifts given to UCL now qualify for the Gift Aid Scheme. This increases the amount of the gift by 28% without any extra cost to the donor. It does so by allowing UCL to claim back the basic rate tax paid by the donor. To qualify for Gift Aid the donor must be a UK taxpayer and his/her combined income and capital gains tax bill must equal or exceed the amount UCL claims back on the gift. The gift can be for any amount and applies to one-off gifts and regular gifts made over a number of years. For UCL to claim the tax benefits the donor must make a "Gift Aid Declaration". One declaration will cover all future gifts and may be cancelled at any time. Cheques should be drawn in favour of "UCL Development Fund". This money is then transferred to the Amyloidosis Research Fund together with the reclaimed tax. If a donor does not qualify for the Gift Aid Scheme or does not wish to contribute in this way, cheques should be made payable to: "UCL Amyloidosis Research Fund".

2014 calendars now on sale All proceeds to the Amyloidosis Research Fund

National Amyloidosis Centre calendars for 2014 are now on sale, produced and donated by John Plant, a patient with amyloidosis and a professional photographer. All proceeds will be donated to the UCL Amyloidosis Research Fund.

The calendar is in a landscape CD case (184 mm x 106 mm) with 14 pages printed in full colour - 1 month per page including cover and rear cover. It is ideal for the office or home and stands on a desk or table. They make perfect "stocking fillers".

Calendars cost £5.00 from Reception at the National Amyloidosis Centre, or £7.50 including postage and packaging (to UK addresses only), if ordered from www.johnplantimages.co.uk. Payments can be made securely using Paypal.

Alternatively, contact John using the contact page on his website and he will call or email you to make other arrangements such as payment by cheque or delivery to addresses outside the UK.

Newsletter funded by a bequest from Laura Lock

2b. Single gift only

I would like to give the following amount

£50 £100 £250 £500 £1,000 £ Other I enclose a cheque/CAF voucher made payable to UCL Development Fund

OR Please debit my Visa Visa Delta Mastercard Maestro CAF card

Name on card

Card no Start date Expiry date

Security code Issue no

Cardholder’s signature Date

UCL Gift form

3. Please complete this Gift Aid section to make your gift go further

If you are a UK taxpayer you may be eligible for Gift Aid which can add 28% to the value of your gift. You must pay an amount of Income Tax and/or Capital Gains Tax at least equal to the tax that the charity reclaims on your donations in the appropriate tax year (currently 25p for each £1 you give).

Please treat all donations I make to UCL on or after the 6 April 2002 as Gift Aid donations until I notify you otherwise.

Signature ___________________________________________________

Date

If you are a higher rate taxpayer you can also claim further tax relief in your Self Assessment tax return. See www.hmrc.gov.uk/charities for more information.

UCL is an exempt charity with HMRC No: X6243

4. Legacy Tick here if you would like to receive information about including the UCL Amyloidosis Research Fund in your will

5. Other gifts Tick here if you would like to be contacted to discuss making a gift of shares, property or land, or other gifts to the UCL Amyloidosis Research Fund

6. Please return this form to:

Beth JonesPA to Professor M B Pepys FRSCentre for Amyloidosis & Acute Phase Proteins Division of Medicine (Royal Free Campus) University College London Medical SchoolRowland Hill StreetLondon NW3 2PFUK

D D M M Y Y

Title

Forename

Surname (family name)

Address

Postcode Country

Data Protection Act (1998): Under the confines of this act, UCL Development & Corporate Communications Office will use the information provided by you for educational, social and charitable purposes only. Your data can be removed from all our mailing lists within one month following receipt of a written request from you. Please contact: Data Protection Coordinator, UCL D&CCO, Gower St, London WC1E 6BT UK.

Thank you for your donation

2a. Regular gift (UK only) I would like to give the following amount £

My gift will be (please tick one)

Monthly Quarterly Annually

for a period of (please tick one) 4 years other

Instruction to bank: Please pay UCL Development Fund, Barclays Bank Ltd Account no 70399159 Sort code 20-10-53 from my account as detailed below:(Office use only) quoting REF NO Name of bank

Branch address

Postcode:

Account no Sort code

Account holder(s) name

Account holder(s) signature(s)

Date

Date of first payment (please allow 4 weeks)

D D M M Y Y

D D M M Y Y

M M Y Y

(Maestro only)(see card reverse)

M M Y Y

1. I would like to support:

the UCL Amyloidosis Research Fund in memory of