Rare diseases 2018 by Mediaplanet UK&IE

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Rare Diseases EURORDIS

Data collection tools and technology are helping in the fight to diagnose rare diseases ONLINE

Gene therapy

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Stephen Hawking “I know it’s possible for people with rare diseases to live good and productive lives” PHOTO: UNIVERSITY OF CAMBRIDGE

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IN THIS ISSUE

Dr Michel van Harten How can Early Access Programmes help patients in need?

What is PAH? The rare heart and lung disease that doctors often misdiagnose

ONLINE

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Patient insight on Autoinflammatory disease: ‘Our bodies are genetically programmed to turn our own defense mechanisms against us.’ ONLINE

Rare disease patients should not be disadvantaged

Rare Disease Day is major event across the globe. The main objective of the day is to raise awareness with policymakers and the public of rare diseases and their impact on the lives of patients. The theme, for the second consecutive year, is research. There are 6,000 known rare diseases and it is estimated that this number grows at a rate of five new conditions each week. For the majority, there are no effective treatments. If this is to change, research will be the key and patient involvement in research will be of fundamental importance. Patients and patient organisations raise funds to support and promote research. They actively ensure research addresses their unmet needs and preferences, providing insights that improve research study design. Patients are the glue that binds together the complex ecosystem of researchers, drug developers, regulators, policymakers and professionals, which allows innovative and more Follow us

effective models of care and treatment into practice. As the date of our withdrawal from the European Union grows closer, it is critical the UK government ensures we remain able to effectively collaborate with our EU neighbours. The number of patients with any given rare disease in any one country is small and so rare disease must reach across national borders. EU regulatory incentives for rare disease medicines have helped deliver almost all of the licenced rare disease medicines in clinical use today. In terms of clinical care, the 24 European Reference Networks (ERNs) for rare diseases bring together a community of over facebook.com/MediaplanetUK

Dr Jayne Spink Chief Executive, Genetic Alliance UK and Chair, Rare Disease UK

“Rare disease research and developments must reach across national borders.”

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900 doctors working in centres of expertise, facilitating the sharing of knowledge and skills, expediting access to diagnosis and treatment. These things must not be lost. Just a few weeks ago, England became the final UK nation to publish its implementation plans for the UK Strategy for Rare Diseases. The plans in our four nations aim to strengthen and incentivise research and improve diagnosis and advance the delivery and coordination of care. With these plans in hand and now more than ever, we must unite across borders, working together across the UK and internationally. We must make sure that patients affected by rare diseases are not disadvantaged. Please Recycle

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The rare disease that made Angela look nine months pregnant After several trips to my GP for something that both she and I thought was relatively minor, I was referred to my local university hospital. To be told that I had Stage IV ovarian cancer and that the outlook was poor was, to say the least, devastating. I didn’t know what to think, I didn’t know what to do. The ‘system’ took over and immediately; I was having appointments with a gynae-oncology surgeon and a Macmillan nurse every week and was placed on the list for a total hysterectomy. My husband and I took our sons out of school for a day and went to Legoland. We didn’t know if that was going to be our last family trip or not. By the fourth week, I could hardly walk - my belly was huge, I looked like I was nine months pregnant. I waddled myself on to the ward for my operation. The surgeon came to see me a day or so after the operation and he looked perplexed. He told me he hadn’t seen anything like it before there were tumours on both ovaries,

(which is apparently really unusual) which were the size of a full-term pregnancy. He removed those. He couldn’t find my appendix and there were tumours all over my abdominal cavity, the bit where your bowels and other organs are. There were tumours on my bowel, my bladder, my stomach, basically everywhere and the remaining space was filled with a jelly-like substance which he called a mucin. He referred me straight away to a medical oncologist for follow up chemo as there was so much that he hadn’t been able to remove. He had only taken out the ovarian tumours and as much of the mucin as he’d been able to. By the time my appointment with

Angela Brook Pseudomyxoma Patient

the oncologist came around, my husband and I had been doing some research online and we had come across a very rare condition called pseudomyxoma peritonei (PMP), which had started with a tumour in my appendix. When we met with the oncologist, he said that the pathology reports confirmed that I did, in fact, have PMP and that there are only two hospitals in the whole of the UK that treat it. A referral to the Basingstoke hospital in Hampshire had already been made, then came the wait for an appointment there and, just over a year after my diagnosis, an operation. Just over a year later, I had a 12-hour operation at Basingstoke hospital, where my spleen, gall bladder the

rest of my momentum and my belly button(!) were removed. I had my bowel resected in several places to remove tumours. Tumours were scrapped off the rest of my bowel, my bladder, my stomach and my diaphragm and I had the capsule covering my liver removed. I then had concentrated, heated chemotherapy poured into my abdominal cavity and ‘sloshed’ around for 90 minutes. I had chemo into my abdomen for four days after the operation. Now, almost eight years after my initial diagnosis, I’m a volunteer and trustee with the charity, Pseudomyxoma Survivor. Read more on healthawareness.co.uk

The support network for those affected by PMP, appendix cancer and peritoneal surface malignancies

Get in touch Whether you're a patient or a caregiver, a medical professional, a fundraiser or a donor, we'd love to hear from you.

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Text 'RARE01 £10' to 70070 to give £10 Texts will be charged at your standard network rate. 100% of your donation will go to Pseudomyxoma Survivor. For terms and conditions, go to http://www.pseudomyxomasurvivor.org/terms-conditions Pseudomyxoma Survivor is a registered charity in England and Wales, number 1143642

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PATIENT INSIGHT

Rare disease gives patient renewed optimism for life By Kate Sharma

“I wouldn’t wish this on my worst enemy, but at the same time it has brought me as much as it has taken away,” says Sammy Harbut, reflecting on life with Cushing’s disease.

It was back in 2007 that Sammy’s sister urged her to visit her GP after a simple bump left her foot black and badly swollen. Tests came back inconclusive, but her health began to deteriorate. She put on weight, and after suffering five miscarriages her periods stopped; she bruised easily and was always tired. “I had checks on my liver, kidneys, heart, blood, respiratory and reproductive systems and they all came back clear,” says Sammy. But by January 2010, she could barely manage the five-minute walk to collect her daughter from school.

Googling her symptoms led to Cushing’s disease diagnosis While Sammy had seen countless specialists, no one had looked at her condition holistically. So, when a colleague put her all symptoms into a search engine, Cushing’s disease came back. Doctors confirmed that Sammy had a tumour on her pituitary gland, causing the production of too much cortisol – the hormone essential in regulating processes such as the metabolic and the immune system. It had to be removed. “Having been used to waiting months for hospital appointments, in July 2010 I asked my endocrinologist if the operation would be before Christmas, to which he replied, “You’ll be dead by Christmas – you’re producing enough cortisol for yourself and another 10 people.”

Sammy Harbut Cushing’s Disease Patient

Reality kicks in It was then that the seriousness of Sammy’s condition hit home. On 12 October 2010, she underwent the surgery. “That day changed my life forever, and the road to recovery has been a long and arduous one at times,” she says. Sammy went from producing too much cortisol, to producing none at all. She now has to take steroids three times a day to stay alive, often gets fatigued and feels unwell, but she has faced the whole ordeal with unrelenting optimism. Since surgery, Sammy has done a parachute jump, gained a university degree, retrained as an occupational therapist and has many new friends living with Cushing’s, who she affectionately calls, “Cushies.” “Life with Cushing’s will always have its challenges, but is worth it all the same.”

Gene therapy shows ‘rare’ promise for the future When it comes to treating rare diseases, gene and cell therapy has come of age and the results are ‘very promising.’

functioning white blood cells and, if left untreated, are unable to fight even common infections. These babies are unlikely to survive longer than a year.

Many rare diseases have an underlying genetic component, and are often the result of a single missing or defective gene. Professor Bobby Gaspar is an expert in paediatrics and immunology at Great Ormond Street Hospital and the UCL Institute of Child Health. When not treating patients, Gaspar develops gene and cell therapies to treat rare diseases of the immune system — diseases such as severe combined immunodeficiency (SCID), where babies are born without

Correcting diseases with bone marrow gene therapy

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“Where the patient’s white blood cells don’t work or develop properly and are causing severe immune deficiencies, we take a sample of bone marrow (full of stem cells) and introduce a working copy of the defective gene into these cells before returning them – now gene-corrected – to the patient. This means their cells now have the right information to grow an immune system that allows their bodies to fight infections

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properly,” says Gaspar. This process is involved in treating diseases like SCID. Since the human genome was mapped more than 20 years, ago, developments in gene and cell therapy have been closely researched and are delivering “very promising” results. Treatment for these rare disorders is currently only accessible at a few specialist hospitals, mainly in Europe and the United States, but now, treatments are being made more widely accessible. “Many rare diseases have limited treatment options but by correcting a patient’s condition using their own cells, we’re able to treat them far more safely than by using the current alternative

treatments,” he says.

Cancer patients could benefit from rare diseases treatments Over the next five years, Gaspar predicts that more gene therapy will be developed for a wider variety of rare diseases, including rare cancers, as well as more common conditions like sickle cell anaemia. As gene therapy becomes more common, patients will be able to access treatment without long — and sometimes arduous — journeys to specialist centres. “Changing treatment pathways will mean that, rather than patients having to travel, cells can be taken and transported to a

Professor Bobby Gaspar Professor of Paediatrics and Immunology, UCL Great Ormond Street Institute of Child Health

“Gene therapy will be developed for a wider variety of rare diseases, including rare cancers.”

manufacturing site where gene modification of the bone marrow cells can take place,” says Gaspar. Once modified, cells can be transported back to the local facility and re-introduced to the patient. One such specialist treatment centre scheduled to open at the end of 2018 is the Zayed Centre for Research into Rare Disease in Children, based at Great Ormand Street Hospital in London. As well as a clinical outpatient department, it will also include a large gene and cell therapy facility as well as research laboratories focused on identifying the genetic basis of a wide variety of rare diseases. “It means effective treatment will be made available to children on a global basis,” says Gaspar.

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Rare disease research helps to ‘join the dots’

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Rare disease networks bring experts to patients As many as 50 per cent of rare diseases are undiagnosed, but international collaboration using digital technology could reduce that figure in the future.

By Victoria Briggs Sandra Courbier Rare Barometer Survey Programme Senior Manager, EURORDIS-Rare Diseases Europe By Victoria Briggs The reality of rare disease is that a correct diagnosis can take years to come by and wrong diagnoses are all too common. Data collection tools and technology are helping in the fight.

There has been great progress in rare disease research, in big part thanks to the advocacy work of the rare disease patient community. Patients are already participating in research, and in some cases, patients have taken the reins themselves to fund their own research. However, the fact remains that there are over 6,000 rare diseases, an estimated 30 million people living with a rare disease in Europe and 300 million worldwide, but no cures and few treatments available for the majority of these diseases. To help change this, patient involvement in research needs to be taken to the next level. The theme for Rare Disease Day 2018 is research. Rare Disease Day 2018 offers participants the opportunity to be part of a global call on policymakers, researchers, companies and healthcare professionals to increasingly – and more effectively – involve patients in rare disease research. Sandra Courbier works for EURORDIS-Rare Diseases Europe, an alliance of over 700 patient organisations representing 30 million people affected by rare disease. Around 40 per cent of rare disease patients have received an inaccurate diagnosis, resulting in them seeing the wrong doctors and receiving the wrong treatments,” she says. “More research will result in improved diagnosis at an earlier stage for more patients.” EURORDIS runs the Rare Barometer survey programme that brings together over 7,000 people affected by rare diseases from around the world to share their opinions on the issues that matter most to rare disease patients. The most recent Rare Barometer survey focused on research and rare disease patients’ participation in research. She cites data collected via these surveys, which help “to put facts and figures on the reality of living with a rare disease.” “Our recent study found that one third of rare disease patients have participated in research, which suggests that there is not enough research to cover the unmet medical needs of rare disease patients. The survey results also show a lack of public funding as the main obstacle to rare disease research.” Read more on healthawareness.co.uk

pecialist treatment is becoming more accessible for patients with rare diseases and the clinicians who treat them, thanks to digital technology which enables expertise to be shared easily across borders. “Technology can help the rare disease community in many ways, mainly by allowing medical expertise to come to the patients, rather than patients having to travel to access expertise,” says Dr Ana Rath, Director of the Orphanet Consortium, an international a group linking 41 countries countries, with the aim of contributing to a rare disease knowledge base to improve the diagnosis, care and treatment of patients with rare diseases. Digital technology means that doctors who have never before seen a case of a rare disease can quickly contact clinicians with expertise in the disease. It also allows medical experts based in geographically dispersed centres of expertise to communicate with each other, and rare disease patients and their families to contact others who are also affected.

Less travel for families to find treatment “A rare disease diagnosis is a bombshell for families and can often disorganise their lives. Sometimes parents must give up work so that they can travel with children to access specialists,” says Rath. “But the advent of telemedicine means consultations can take place on screen, at a local medical centre, which is a benefit for both families and doctors.” Technology also makes it easier to share data, which will help with rare disease diagnosis. Rath says: “Geneticists now say that as many as 50 per cent of

Dr Ana Rath Director of the Orphanet Consortium, Inserm US14 - Orphanet

“Technology can help the rare disease community by allowing medical expertise to come to patients, rather than patients having to travel to access expertise.” rare disease cases are undiagnosed. To define, name and diagnose rare diseases, we need large amounts of data, and technology enables us to collect, access, and share it. It will enable us to find more cases, so more information about them can be pooled, to the advantage of patients, doctors and researchers.”

International developments help EU patients Hospitals that house centres of expertise in various specialities are now beginning to come together to form European Reference Networks (ERNs) – virtual networks involving healthcare providers across Europe. They aim to facilitate discussion on complex or rare diseases and conditions that require highly specialised treat-

ment and concentrated knowledge and resources. “These networks of expertise, which will cover various types of rare diseases, will enable patients in the EU to access experts based in other EU member countries,” says Rath. The first ERNs were launched in March 2017, involving more than 900 highly-specialised healthcare units from over 300 hospitals in 26 EU countries. Twenty-four ERNs are working on a range of thematic issues including, amongst others, bone disorders, immunodeficiencies, childhood cancer, inherited and congenital malformations and rare intellectual disabilities.

Cross-border consultations have now started This infrastructure enables the review of a patient’s diagnosis and treatment by ‘virtual’ advisory panels of medical specialists across different disciplines, using a dedicated IT platform and telemedicine tools. It will mean that patients can take advantage of international expertise without having to travel to access it. “The platform for sharing data and enabling tele-consultations was launched late last year and so far about 50 patients have had consultations,” says Rath. A second call for more hospitals willing to join the existing ERNs went out this year, so they are expected to grow. Similar networks, mainly based around rare diseases research, also exist in the USA, and there is potential for transatlantic collaboration. Rath says: “Technology is making this an interesting time for research and treatment of rare diseases in Europe, and patients are already starting to benefit.”

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Children with rare diseases find their lives disrupted by treatment By Linda Whitney

Centralised treatment for children with rare diseases looks to end the misery of multiple different appointments.

“A child with a rare disease will often need multiple clinic appointments, which means a lot of travel. This can disrupt their education, their friendships, and it can also cost a deal of money. In some cases, a child’s parents must stop working, thus impacting the family’s quality of life,” says Dr Larissa Kerecuk, Rare Disease Lead, Consultant Paediatric Nephrologist at Birmingham Women’s and Children’s NHS Foundation Trust and Paediatrics Lead for NIHR in West Midlands. In order to reduce these financial and emotional burdens, a ‘centralised’ approach to care is being trialled. Birmingham Children’s Hospital began trialling the centralised ap-

proach in 2016 with clinics for tuberous sclerosis – a rare genetic condition causing benign tumours in different body parts such as the brain, skin, kidneys and heart. Now, children can see specialists such as neurologists, nephrologists, psychologists and researchers all in one place.

Children involved in designing the clinic to fit their needs “Patients and their families were involved in designing the service from day one, as they are the experts in what is needed,” says Kerecuk. “We reached out to them through hospital visits and social media to seek their opinions.” The centre has a large room where families can meet others living with rare diseases, a play area for children and siblings. There is a sensory room,

“A child with a rare disease will often need multiple clinic appointments, which reduces their quality of life.”

Dr Larissa Kerecuk Rare Disease Lead, Consultant Paediatric Nephrologist, Birmingham Women’s and Children’s NHS Foundation Trust and NIHR Clinical Specialty Lead for Paediatrics, West Midlands

a teenage room and a quiet room for sensitive discussions. Families have access to Roald Dahl Rare Disease Specialist Nurses who can offer advice, coordinate appointments and signpost services. Representatives from Patients’ Charities attend to help at no extra cost to the NHS. On-site research coordinators offer patients the chance to join studies, increasing the number of families who join, and speeding up research. The service’s patient support days, where families of children with many different rare diseases meet and talk, have grown into events that attract hundreds of people from all over the world. “In our consultations, patients and families say that they like the onestop-shop approach,” says Kerecuk. “The most common comment is, ‘Why wasn’t this done before?’”

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Rare diseases shed light on more common conditions By Kate Sharma

Rare diseases struggle to gain the interest of researchers and funders of research, but they often help understand of more common conditions, opening new doors for therapy.

“The clinical side of things has always been the same – mainstream medicine has never taken much of an interest in rare diseases,” explains Professor Timothy Cox, Director of Research, Honorary Consultant Physician, Emeritus Professor of Medicine, University of Cambridge. “It takes a doctor who likes to take on challenges posed by patients who are difficult to diagnose.” Really this is much more an attitude of mind and a way of practice than a matter of huge specialist knowledge.

Government investments encourage ongoing research However, an enthusiastic doctor alone won’t bring the treatment that desperate families long for – that takes much broader collaboration between academics, clinicians, companies and patient groups. So, to help incentivise the development of drugs for rare diseases, the UK government adopted the European Orphan Drug Act in 2001. While the act has certainly made a significant difference – Cox doesn’t think it goes far enough to stimulate broader academic research that could help patients of rare diseases while also advancing medical knowledge as a whole. “It does give incentives and has helped introduce many new drugs, but it hasn’t yet supported very much additional research out-

in a population. Such knowledge provides the building blocks of information essential to better diagnose and treat not only ultra-rare Gaucher disease but also can be explored in Parkinson’s, which is far more common within the general population. Professor Timothy M Cox Director of Research, Honorary, Consultant Physician, Emeritus Professor of Medicine, University of Cambridge

side of industry,” continues Cox. “Finally, the Act lacks teeth, since it cannot ensure that all European countries will pay for drugs that have been approved – in that sense European Law falls short of patients’ and companies’ expectations!”

Parkinson’s benefits from rare disease discoveries Further research into rare diseases could have much more impact in healthcare in general. A great example is research currently being conducted into Gaucher disease – a very rare condition that causes inflammation in the liver and spleen and bone marrow. Researchers recently discovered that mutations in same gene that is involved in Gaucher disease are also strongly implicated in Parkinson’s disease so that novel treatments might be shared across rare and frequent consequences of genetic variation

Rare disease patients offer themselves for clinical trials Perhaps the unsung heroes in the research world are the patients themselves. Many are living with the pain, trauma and daily struggle of an incurable illness and yet make themselves available for clinical trials and investigations to develop treatments they will never benefit from personally. “Patient advocacy groups are incredibly important,” concludes Cox. “It was a patient organisation in the US who first gave incentives to companies and investigators to research and discover effective therapies for cystic fibrosis. That’s an extreme example, but sometimes a driven patient will initiate the set up of a small drug trial that proves successful or build a patient registry.” ‘The goals of patients, clinical scientists and doctors are the same – it is the coming together to solve the long and tortured business of drug discovery, development and approval that is so crucial today’. Exciting developments are certainly taking place in the realm of rare and ultra-rare diseases and genuine collaboration based on trust and respect can only help to enhance that.

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20 years ago, ‘rare’ often meant ‘incurable’

How far have we come in the field of rare and genetic diseases since the 1990s?

Back in 1990, rare and genetic diseases were on the margins of healthcare systems in most developed health economies. Clinical genetics was a very small, rather obscure specialty of interest to a few academic clinicians fascinated by the intellectual challenge that genetics offered. For most clinicians, and indeed service planners too, ‘rare’ was synonymous with ‘incurable’; and, not many people affected meant it was not very important in the overall delivery of healthcare. For patients and families, medicine had little to offer

apart from the palliation of symptoms and the possibility of exercising reproductive choices where a genetic disease was suspected. Since then we have travelled a long way – rare and genetic diseases increasingly occupy centre stage in the planning and delivery of future-facing health care. Diseases that were formerly incurable and lethal are now often better managed, and although the absolute numbers of disease modifying therapies for rare conditions remains small, advances in science give real hope of progress to growing numbers of patients and families. Rare and genetic diseases are now known to be complex, multi-system disorders that require input from a network of different specialists

One voice for the millions in our country affected by a ‘rare disease’

GZUK.XLSD.18.01.0025 Date of preparation: February 2018

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if they are to be managed in ways that deliver the best possible outcomes for those affected. The onus now for the planners and providers of health and social care is to demonstrate that they have the flexibility and the will to manage this complex ecosystem in the best interests of the patients and families who rely on it. It has been my privilege to be the Director of Genetic Alliance UK since 1993, stepping back from this role in 2017. To help give a voice to those with rare and genetic disorders, so that those with the power to make positive changes were able to hear, understand and act on the issues patients and families were facing, and in many cases still are, has been a challenge and a joy. An estimated

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6,000 children are born every year with a syndrome without a name and the ongoing support for children and their families has been a privilege to be a part of. It would not have been possible to achieve anything without the commitment, support and sheer hard work of a fantastic team of trustees, colleagues. There have been many milestones that help measure out progress we have made over the years. In 1998 we pushed for the adoption of Orphan Medicinal Product Regulations across the EU – incentivising the development of medicines for rare diseases, while 2009 saw us celebrating Rare Disease Day with parliamentary receptions across the UK – now an important annual event

Alastair Kent OBE Ambassador, Genetic Alliance UK

“Rare and genetic diseases increasingly occupy centre stage in the planning and delivery of future-facing health care.”

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in the political calendar. Rare Disease Day has helped galvanise support amongst the general public and policy makers across the UK. The UK Strategy for Rare Diseases, published in 2013 marked the first time the four UK governments had a specific policy targeted at meeting the needs of our members and families, and we have played a key role in supporting the delivery of this strategy across the UK. Today we see the NHS planning a genomic medicine service that will bring cutting edge science to serve the needs of patients and families. Read more healthawareness.co.uk

The One Voice Choir – made up of members of Parliament, members of the House of Lords and the patient community – stands together today, on Rare Disease Day, at London’s Westminster underground station to raise awareness of the impact of living with a rare disease and foster global collaboration in rare disease research. All patients should have access to life improving treatments and innovation, being rare doesn’t have to mean we don’t care. This event has been organised by Sanofi Genzyme. Watch the MPs rehearsing for the big day by scanning the code with your smartphone.

Tweet your support to @rarediseaseday using #onevoicechoir and/or #rarediseaseday

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PATIENT INSIGHT

Jaclyn Caisley aHUS Patient

Theimportanceofearlydetection with aHUS patients By Alex van den Broek Jaclyn Caisley went from being a ‘normal person with a normal life,’ with no significant medical history, to living with a life-threatening condition in just two weeks.

In September 2013, Jaclyn Caisley entered the new school year as a young, impassioned teacher suffering from what she suspected as simply ‘the holiday blues.’” Yet, this initial case of laryngitis happened to be the trigger to a life changing illness. “You think, ‘I’m 25, I’m just a bit sick,” said Jaclyn. However, in a short period of time, while waiting for the results of general blood tests, her condition drastically worsened. “I had been sick for two weeks straight. I woke up one day and I was yellow… I couldn’t stand up!” Having been rapidly transferred to the Urology Department at Freeman Hospital, she underwent a succession of X-rays, blood tests, ultrasounds and a kidney biopsy where it was discovered she had just three per cent kidney function. The accumulative results lead to a diagnosis of Atypical Haemolytic Uraemic Syndrome (aHUS) of which she had no family history. “I thought, how can I have something I have never even heard about? Everything happened so quickly; from being a perfectly healthy 25 year old to spending the next six weeks in hospital, barely able to stand and needing help to wash and dress,” said Jaclyn.

Treatment and recovery The recovery process involved just nine sessions of dialysis; crucially with the continued use and access to medication. “The medical care was outstanding. By January 2014, I had regained 30 per cent of my kidney function and today that stands at around 80 per cent of normal function. I was incredibly lucky to be diagnosed so quickly.” Now, back in the classroom, with just a two-hour fortnightly treatment in the comfort of her own home, Jaclyn has regained quality of life and hope for the future she never thought she would have. “That is what has made the difference to my future, my life and my health.” With plans to marry in the summer and continuing work at her secondary school, doing what she loves, Jaclyn admits, “I never thought it would be like this.”

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Breakthrough treatment reduces risk of kidney failure By Kate Sharma

A rare, and potentially fatal condition, aHUS, mystified doctors for years. Today, thanks to patient support, the outlook for sufferers is much more hopeful.

With just 210 diagnosed cases in the UK, atypical haemolytic uraemic syndrome (aHUS) is an extremely rare condition that causes kidney failure. It is distinct from the more common form of haemolytic uraemic syndrome, which is caused by some types of E. coli. With symptoms including tiredness, headache and decreased urine output, aHUS is difficult to diagnose and, until recently, even harder to treat. “The problem was, we didn’t know what caused

the condition,” says Professor David Kavanagh, Consultant Nephrologist at the National Renal Complement Therapeutics Centre (NRCTC). “If patients around the country hadn’t donated their DNA, we’d be none the wiser.”

Genetic faults cause patients’ bodies to attack themselves In 1998, after studying samples from aHUS patients, the team at the NRCTC discovered the condition was linked to the body’s complement system – part of the immune system that fights infection. Complement is a defense system centred around a substance called C3, which coats and destroys viruses and bacteria. Our bodies

naturally produce protector proteins that inactivate the C3 to prevent it from attacking our own bodies. However, some people have a genetic fault that prevents these proteins working. “Over 60 per cent of patients who had aHUS have a genetic fault that prevents them from producing the protector proteins,” explains Kavanagh. “As a result, the C3 attacks their own cells.” As complement attacks the body’s own cells, especially those that line the blood vessels, it leads to clots in the filters of the kidney, putting the patient at risk of kidney failure. Until recently, the outlook for patients with aHUS was bleak. There was no cure and a kidney transplant wasn’t usually possible

DELIVERING BREAKTHROUGH INNOVATIONS FOR PATIENTS WITH RARE DISEASES Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the innovation, development and commercialization of life-changing therapies. Patients with rare diseases often have no effective treatment options, and they and their families suffer with little hope. Our goal is to deliver medical breakthroughs where none currently exist. /UNB-U/18/0004 February 2018

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as the disease would attack and destroy the new kidney. A lifetime on dialysis was the only option.

A new drug overrides the body’s self-destructive gene However, in 2011 fresh hope was given when a monoclonal antibody was licenced to treat aHUS patients. The drug works by blocking the complement system and therefore preventing it from damaging the body’s own cells. “Initially patients receive it every week and then every two weeks,” says Kavanagh. “It has revolutionised the management of the condition. Eculizumab usually prevents patients developing kidney failure and allows patients already on dialysis to receive a kidney transplant without a recurrence of disease.”

Although very effective, Eculizumab does suppress the immune system leaving patients susceptible to infections, such as meningitis, and the patients therefore need vaccinations and life long antibiotics to prevent this.

aHUS is an inherited condition As with many medical intervention – the sooner treatment can begin the better. “Because it is an inherited condition, relatives of aHUS patients with complement mutations may be at risk of disease. We can now see all relatives and perform tests to see if they are at risk of disease too. If they are we will give them an aHUS at-risk card” says Professor Kavanagh. “If they feel unwell they can go straight

“It has revolutionised the management of the condition. It takes less time and we have fewer patients needing transplants.”

Professor David Kavanagh Consultant Nephrologist, National Renal Complement Therapeutics Centre (NRCTC)

to their GP, who can give them a simple blood test and, if they are abnormal, they’ll give us a ring so we can treat them early, thus preventing kidney failure. The same patients who played a critical role in the research which ultimately resulted in a treatment for aHUS are now playing a pivotal role in protecting their family members. By asking them to get tested and bringing them to aHUS roadshows to learn about the early symptoms of disease, treatment can be initiated early to prevent kidney failure when the disease strikes.

Read more atypicalhus.co.uk

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How the rare genetic disorder, NAIT, has affected my family

The rare condition that causes fits and even deaths in babies Hypoparathyroidism causes challenging symptoms in children and adults and can often be misdiagnosed, even as a psychiatric illness, but greater awareness and an available treatment can change lives.

When her baby began having seizures, for which doctors could not initially find a reason, Sophie* talked to her family and uncovered stories of other children who started shaking and then died. More tests showed her child had hypoparathyroidism, a rare condition caused by low levels of the parathyroid hormone (PTH), which regulates calcium metabolism. Given treatment with active vitamin D to raise the blood calcium to normal levels, her child soon recovered. Professor Rajesh V Thakker, May Professor of Medicine at Oxford University, says: “Hypoparathyroidism – hypopara – is triggered when the parathyroid glands, which lie next to the thyroid gland in the neck, fail to make enough PTH, which is the body’s calcium regulator. “The blood in an adult contains about two teaspoons of calcium, and even a minor change can have consequences. Too little causes tiredness, aches, cramps and foggy thinking, and I have seen patients misdiagnosed with depression. Severe hypocalcaemia causes epileptic fits and death.”

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Professor Rajesh V Thakker May Professor of Medicine, University of Oxford

Causes The most common cause is surgical removal or damage to the glands, but they can also be destroyed by the body’s own immune system. Genetic problems may also result in absent or malformed glands. “Hypoparathyroidism can be hard to spot – I’ve seen patients in whom it has gone undiagnosed for years,” says Thakker. Low blood calcium can also result from other causes, so tests are needed to diagnose hypoparathyroidism. Initial treatment is with an active preparation of Vitamin D, which regulates calcium absorption, plus calcium tablets if required. If that fails, patients may be offered injections of synthetic PTH. However, where there is a problem with the calcium-sensing receptors, another drug may work, but it requires trials, and so far, doctors and patients groups have not succeeded in securing one. *Actual name altered for anonymity

A devastating brain bleed caused by NAIT (Neonatal Alloimmune Thrombocytopenia) while still in the womb, left my son with lifelong disabilities.

At 35 weeks pregnant, I was in a car accident and admitted to hospital. An ultrasound scan on my unborn baby found extensive bleeding on his brain. An emergency caesarean section was performed and Archie was born. He had black eyes and was covered in bruises. He had a platelet count of only 9k. A normal human platelet count is between 150-450,000/µl. Platelets are essential for healing when severe trauma is caused. They allow blood to clot, rather than bleeding endlessly and causing permanent damage. Subsequent testing of mine and my husband’s blood identified a mismatch between our platelets and a diagnosis of NAIT was given. My body had formed antibodies against Archie’s platelets and destroyed them. The following day, we were told the extent of Archie’s brain damage. Around 75 per cent of his brain had been destroyed. We were told he would never walk or talk and prognosis was guarded. Archie spent a month in hospital having treatment to stabilise his platelet levels. Any future pregnancies for us would have a 50 per

Archie Magee NAIT Patient

cent chance of NAIT re-occurring but treatment to prevent this was available. Archie is eight, now, and severely disabled. He has cerebral palsy, visual impairment, epilepsy, learning disabilities and challenging behaviour. He attends a special school, is tube fed and uses a wheelchair. Despite his disabilities, Archie loves life; he has an amazing sense of humour and character. He has good understanding, a brilliant memory, can say a few words and can mobilise in his walking frame. Thanks to the advice and support of the charity, naitbabies, we decided to have another child. An amniocentesis determined that our unborn daughter also had NAIT. Treatment began at 12 weeks of pregnancy and involved weekly transfusions of immunoglobulin and steroids. Essie was born by planned C-section at 34 weeks. She had a platelet count of 84k. Her platelet level bounced up to normal levels without treatment and she is now a happy, healthy five year old. Screening for NAIT should be standard and routine.

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Making science work for rare disease patients

Mike Thompson Chief Executive of the Association of the British Pharmaceutical Industry (ABPI) The UK can be a leader in rare disease research and NHS patients can reap the benefits.

Rare diseases are some of the hardest conditions to develop medicines for and the basic science has lagged behind our ambition to find cures and treatments for many years. Now, scientific advances, like genetic testing, mean we have a better understanding of the root causes of these debilitating and often fatal conditions. The bio-pharmaceutical industry continues to pioneer the science that we hope will ultimately solve the complex challenges of researching, developing and clinically testing rare disease treatments. The fact that 75 per cent of rare disease affect children – with a third of patients dying from their condition before their fifth birthday – drives our scientist to find the treatments and cures that these patients need. However, the challenge is immense, and we need to be realistic about the time and money it takes, especially when these small groups of very young patients are spread out across the UK and Europe. We have already seen huge breakthroughs in the last year alone: early clinical trials in gene therapy have given hope to haemophilia patients; scientists have found a way to supress the build-up of harmful proteins in patients suffering from Huntington’s disease and we have seen a CAR-T therapy launched to use a patient’s own immune system to fight rare types of cancer. These innovations for diseases that we once thought incurable are just the start of our efforts to find treatments for all 7,000 to 8,000 recognised rare diseases. But finding cures is only half of the success story and the UK must look beyond pioneering the science to making sure NHS patients are very first to benefit from the breakthroughs we foster. There is a lot more we collectively need to do, working as the pharmaceutical industry and the government together at a national, regional and local level to make sure UK patients have access to these breakthroughs in line with, or in advance of, their counterparts in Europe. It isn’t just about being transparent about the process for making these treatments available, but also changing the way we assess these medicines to be worth investing in, beyond the individual benefit to the three million people affected by a rare disease in the UK, for society as a whole. The future is exciting, and if we get this right, the UK has the potential to be a global leader in cutting-edge rare disease science, with NHS patients the first to benefit from the research and development our companies are pioneering. Read more on healthawareness.co.uk

There are high costs to develop drugs that may only help a few people With the NHS under unprecedented financial pressure it’s more important than ever that new drugs developed to treat rare diseases also deliver value-for-money for the NHS.

By Kate Sharma

heela Upadhyaya leads the team at NICE, which runs the programme to evaluate treatments for very rare diseases and decide whether they should be funded by the NHS. The approval process for rare disease drugs is very different from the process in place for therapies to treat more common conditions. With such a small population base, the evidence on how well a drug works can be considerably limited. “What we see is that there are often gaps in the evidence,” says Upadhyaya. “In many cases we have a lack of information about the natural history of the condition so we don’t know how it progresses. With the short duration of follow-up studies we also lack the data to show what happens in five or ten years.” Therefore, a number of assumtions have to be made on what may happen, based on the evidence presented, which makes the job a harder one.

The value of rare disease drugs can be hard to qualify It is a harsh reality that money plays a significant role in whether or not drugs come to market. NICE assess the value-for-money of new medical interventions based on how much it will cost for each additional quality-adjusted life-year (QALY) a particular intervention will give to a patient. When it comes to rare diseases, the situation is further complicated by the fact that many drugs don’t simply

exactly what a difference the therapies make,” says Upadhyaya. Taking all this into account, drugs for rare diseases are evaluated against a sliding QALY scale starting at £100,000 per QALY and rising to a maximum of £300,000, which is 10 times higher than the normal threshold used in NICE’s standard technology appraisal programme . Sheela Upadhyaya Associate Director of the Highly Specialised Technology (HST) Programme, National Institute for Health and Care Excellence (NICE)

“There has to be more we can do together.” keep patients alive, they dramatically improve life. This is often impossible to measure so patient experience plays a key role in the evidence presented. “Clinical and patient experts play a massive role in providing supporting evidence by telling the committee

Some drugs are too costly to bring to market Of course, there are a lot of drugs that either don’t have sufficient supporting evidence or remain far too expensive to bring to market. In response, NICE encourages time-limited management access agreements, agreed with the NHS, companies, clinicians and patient groups. These agreements commit to addressing gaps in evidence, clarifying uncertainties and securing commercial agreements that will manage the financial risks for the NHS. As part of this agreement, patients can continue to access treatment while evidence is gathered. “It’s important that people know that we don’t want to say no,” says Upadhyaya. “We are in a challenging space with trying to review a limited evidence base, budgets squeezed to the maximum and more and more drugs being developed. If we collaborate with companies and clinical and patient experts, we can make this work. There has to be more we can do together.” Read more on healthawareness.co.uk

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This article was developed in collaboration with Actelion Pharmaceuticals UK who also provided funding. Contributors to this article did not receive payment for their involvement.

The rare heart and lung disease that doctors often misdiagnose By Victoria Briggs

Dr Luke Howard Consultant Pulmonologist, London Imperial College Healthcare NHS Trust

“Its not unusual for doctors to mislabel the condition” What begins as breathlessness, and is often confused with more common respiratory diseases like asthma, can turn out to be a rare and potentially deadly heart and lung condition. Early diagnosis and access to the right treatment is vital for those affected. Pulmonary Arterial Hypertension (PAH) is a rare and progressive illness with symptoms that can be overlooked or mistaken by doctors for other more common disorders such as anxiety, asthma, or even heart disease. Caused by high blood pressure in the pulmonary arteries, PAH is a life-threatening condition that often first appears as breathlessness. “Symptoms often appear during exercise,” says Dr Luke Howard, Consultant Pulmonologist at London’s Imperial College Healthcare NHS Trust. “People or doctors can put their breathlessness down to the fact that they may be unfit, until eventually they start to become breathless during everyday activities.”

More women are affected than men Over 3,000 people in the UK are living with managed PAH, with many more thought to be living with the disease undiagnosed. Affecting around twice as many women as men, the average age of onset occurs in a patient’s 40s. Symptoms can appear vague – so much so that it’s not unusual for doctors to mislabel the condition.

As well as breathlessness, other symptoms of PAH can include dizziness, blackouts, swollen ankles and a feeling of tightness in the chest. In advanced cases, the veins in the neck can also appear distended. “The condition is caused by a narrowing in the smaller blood vessels of the lungs. The narrowing leads to a decrease in blood flow, which puts pressure on the heart as it pumps harder trying to get the blood through,” says Howard. “Ultimately, the heart cannot cope.” Unlike coronary heart disease, when fatty deposits build up inside the arteries, in the case of PAH, it is the cells that line the blood vessels that begin to proliferate, causing them to block.

Untreated survival rates are two to three years Without treatment, the prognosis for patients is worse than many cancers – average survival rates for some types of PAH are between two and three years. Although PAH is incurable, developments in treatment can extend survival by up to several years. “Oral drug therapies have greatly improved treatment for PAH,” says Howard. “It means more people are surviving with it, than dying from it.” But there is still room for improvement when it comes to treating the condition. Howard stresses the importance of patients attending specialist treatment centres with expert staff, the latest diagnostic techniques and access to advanced treatments. “These complex and expensive drugs for PAH are restricted to specialist centres which means that only specialist centres can provide the full range of treatment options to patients. Outside these centres there is a risk that patients may be undertreated or sometimes even inappropriately treated.” “We need to make sure patients are in the right place. My plea to doctors is that if it doesn’t sound like asthma, in that there’s no wheezing or coughing, then it probably isn’t asthma. Send patients to an undiagnosed breathlessness clinic where they can be seen by a cardiologist or a respiratory specialist,” he advises.

WORKING TOGETHER TO IMPROVE PATIENT OUTCOMES IN PAH Actelion is committed to improving the lives of those affected by pulmonary arterial hypertension (PAH). We believe that by working together with healthcare professionals and patient organisations we can help to reduce the time to diagnosis and achieve better outcomes for patients.

ACTELION PHARMACEUTICALS UK LTD Chiswick Tower 13th Floor. 389 Chiswick High Road, London W4 4AL UK Phone +44 (0) 208 987 3333. Fax +44 (0) 208 987 3322 NOP 18/0392. Date of preparation: February 2018

Financially penalised for having PAH

Dr Iain Armstrong Chair, Pulmonary Hypertension Association (PHA UK)

In addition to the physical and emotional fallout of the diagnosis, there can be a financial impact too. The disease most commonly strikes in middle age. By default, those affected, are often the breadwinners of the family. Almost overnight, working lives can come to an end as independence is lost. “As well as having to give up work, those with PAH find they can no longer get mortgages or life insurance,” says Armstrong, explaining that it can also be a struggle to get disability and sickness benefits due to the rarity of the condition and the fact that it isn’t always recognised.

“PAH affects your ability to carry out normal, everyday activities” Pulmonary Arterial Hypertension patients feel like their body has let them down. What’s worse, with this rare disease, there’s nothing to see. A diagnosis of Pulmonary Arterial Hypertension (PAH) can be devastating, not just for the individual affected but for the patient’s family too. “Those with the condition go from being independent to becoming very limited in their everyday activities. PAH affects your ability to go shopping or climb stairs — even washing and dressing can become difficult,” says Dr Iain Armstrong, Chair of the UK’s Pulmonary Hypertension Association (PHA UK), an organisation that provides support for sufferers. “Many feel that their body has let them down.” What is already a difficult situation can be exacerbated by the fact that a patient with PAH can look absolutely fine. “Compared with other life-threatening conditions, there’s nothing to see,” says Armstrong. “People find that others don’t understand their condition. They end up feeling fraudulent, or that they’ve let everybody down.”

IMAGE: ISTOCK.COM/SVETIKD

Diagnoses can take up to two years The rarity of PAH means that even getting an accurate diagnosis can prove to be an uphill battle. In a recent survey, half of those with the condition had to wait at least a year, seeing as many as five specialists in the process, before a diagnosis could be made. “The effect on patients is that they lose faith in the system. They end up feeling like they’re being passed around,” says Armstrong. The good news is that once a diagnosis is made, there are specialist centres around the country able to provide patients with effective treatment and support. As well as drug therapies to suppress symptoms, treatment centres also provide patients with vital rehabilitation services, helping them to lead active lives for longer. “With targeted treatment, the trajectory of the disease can be significantly improved with survival times of up to eight years after diagnosis or even longer in some patients. This may be because new treatments and tools, are helping to change the picture, such that these exceptions are starting to become more common,” he says. PAH 18/0474 Date of prep: February 2018

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Diane and Ella tell their neurofibromatosis story “I am 13 years old. When I was eight, I was diagnosed with neurofibromatosis,” writes Ella, who celebrates her 14th birthday in March. “It’s given me scoliosis, three brain tumours, and hyperpronation. I am scared for what the future holds for me, but, as I told my support worker, “I can’t change it, so I will have to roll with it and do my best to have a good life.”

It is heartbreaking for her mother Diane, to see the maturity and grace with which her teenage daughter is handling this difficult diagnosis. Recounting the early stages of Ella’s diagnosis, Diane describes the difficult time as life-changing. “2012 was a year that changed our lives forever. After exhausting tests over many years, the paediatrician

said Ella had neurofibromatosis Type 1. He knew little about it and had to quote from the internet, as did our GP when I went to visit them for support.” One of the main problems with neurofibromatosis is how little it is known, even among medical professionals. Sadly, Diane and Ella’s story is not unique. Like her Doctors, Diane turned to the internet: “When faced with no practical medical support you’re only left with the internet. With hindsight, this was the worst thing to do, as you are faced with images showing worst-case scenarios.” This is especially true with conditions as variable as neurofibromatosis, which can sometimes involve external tumours under the skin called plexiform fibromas. Diane continues: “During this

Ella Sunderland

Neurofibromatosis Patient

“I am scared for what the future holds for me, but, as I told my support worker, “I can’t change it, so I will have to roll with it and do my best to have a good life.”

period, I can only say we were in a very dark place. We were passed onto Carolyn, a specialist neurofibromatosis nurse with The Neuro Foundation. “Out of the blue, late one morning, the phone rang, and a voice said: “Hi, is that Mrs Sunderland? I’m Carolyn from The Neuro Foundation; I just wanted to see how you are all coping.” During this awful time, that was the first time anyone had asked.” Carolyn is part of The Neuro Foundation, who rely totally on public donations to provide the specialist advice network, a crucial arm of the charity that provides support and advice to people like Diane and Ella. Experts in the field of neurofibromatosis, they understand how variable the condition is, but also how people want to live their life.

Reflecting on the impact of Carolyn’s support, Diane says: “Of course, the diagnosis hasn’t changed, but Carolyn has been able to be positive and prove that – with the right care and support – those with neurofibromatosis can have a fulfilling life. Carolyn been into every school Ella has attended and educated those involved in her care and made sure they understand the complexities of neurofibromatosis. Ella is excelling at school and I know, if I am ever in doubt, I can rely on Carolyn to point me in the right direction. I wish everyone with neurofibromatosis could have a ‘Carolyn’!”