New research reveals impact of ‘hidden’ health conditions and calls for better care for patients with rare disease, PKU
For the first time, patient groups – supported by funding from BioMarin - from across six countries in Europe have come together to create a coalition with the shared goal of improving health services for PKU patients. The Live Unlimited PKU campaign has launched on the 28th June, International PKU Day and brings together patient organisations from Turkey, Spain, France, Sweden and Italy to tackle public misconceptions of the disease.
The campaign aims to raise awareness of the potential severity of the disease and calls for improved standards of adult care, including consistent provision of metabolic specialists, dieticians and psychological support for every adult with PKU in Europe – aligned with the European Guidelines from 2017.iv
Phenylketonuria (PKU) is a rare, lifelong metabolic condition which affects around 1 in 10,000 people in Europe.ii The condition limits a person’s ability to break down protein, with potentially devastating effects on the brain if left unmanaged.iii In Europe, the condition is screened for during the new born heel-prick test, but just 9 per cent of the public have heard of the condition.iv
There is currently no cure for PKU, so either a heavily restricted diet – with almost no natural protein - and/or medical treatment may be required for life.v Despite the neurological effects of the condition and difficulties following a low-protein diet, just 12% of adults with PKU have access to the multidisciplinary tools and support they need, with many adults having to go to children’s wards to receive any specialist care.vi
PKU can have a serious and long-lasting effect on patients’ mental health and quality of life, with a recent study showing that as many as 52% of adults with PKU lived with anxiety or depression. Other issues reported by patients include ‘brain fog’, sleep issues and lapses in concentration.vii
These findings were in line with polling results conducted as part of the campaign, which demonstrated that PKU patients are more likely to find certain life milestones stressful than people without a hidden health condition. Key findings build a Pan-European picture of the impact PKU has on the lives of patients when compared to those without a hidden health condition, including:
Every patient is entitled to the best possible care regardless of the rarity of their disease. The Live Unlimited PKU message resonates with us as healthcare professionals, with patients and hopefully, with the general public and decision makers. Raising awareness of this condition and the burden it has on patients’ lives on a daily basis is extremely important.
The Live Unlimited PKU campaign has been co-created by many patients, and six patient support organisations - with funding and support from the biopharmaceutical company BioMarin - in order to drive policy change and help put in place the right care for adults living with PKU across Europe.
The campaign includes a suite of visual imagery and videos featuring the personal stories of patients across Europe. There are campaign videos which highlight the lives and challenges of PKU patients in their respective countries and many more case-studies available on the campaign website (www.liveunlimitedPKU.com). The one-year campaign will run until International PKU Day 2020, with many patient groups and individuals helping to raise awareness of PKU until this date. Further events and initiatives will continue throughout the year.
Five patients from across Europe share their experiences of living with PKU in a series of videos. The full video series can be viewed here.
About Live Unlimited PKU
The Live Unlimited PKU campaign launched in June 2019 to raise awareness of the gaps in care for adult patients living with the rare genetic condition, phenylketonuria (PKU). The campaign has been developed alongside the six patient groups and their memberships: AMMeC and Cometa A.S.M.M.E (Padua) (Italy), Les Feux Follets (France), Svenska PKU-föreningen (Sweden), PKU Aile Derneği (Turkey), and FEEMH (Spain), funded and developed by BioMarin Europe Ltd. The campaign seeks to call for consistent provision of adult metabolic specialists, dieticians and psychological support for every adult with PKU in Europe.
About phenylketonuria (PKU)
Phenylketonuria (PKU) is a rare, lifelong metabolic condition which limits a person’s ability to break down protein and can lead to cumulative toxic effects on the brain.iv With PKU, the foods you eat directly impact the way your brain functions.
People with PKU have a problem with the phenylalanine hydroxylase (PAH) enzyme, and so can’t fully break down an amino acid called Phenylalanine (Phe), which is found in all protein-containing foods (e.g. nuts, meat, eggs, dairy) and sweeteners such as aspartame.iv If too much protein is consumed, high levels of Phe build-up in a person’s blood and disrupt the balance of neurotransmitters - or even cause physical damage to the brain itself. This can result in neurological symptoms such as problems with memory and attention, depression and anxiety.[viii] The condition is screened for during the new born heel-prick test, and affects around 1 in 10,000 people in Europe.iv,v PKU is an inherited autosomal recessive disease. This means that if both parents are carriers of the PKU gene, their baby has a 1 in 4 chance of suffering from PKU.[ix] The condition is tested for in almost all European countries during the new born heel prick test, but general awareness of the condition remains low. Until fairly recently, doctors thought that PKU was a condition that was outgrown once the brain fully developed as a teenager. However, we now know that high blood Phe levels continue to result in damage at any age, and so the condition should be managed for life.[x]
Please find the campaign website, including all patient stories, here: www.liveunlimitedPKU.com
[ii] ESPKU. PKU: Closing the Gaps in Care An ESPKU benchmark report on the management of phenylketonuria within EU healthcare economies. Available at: https://www.espku.org/wp-content/uploads/2015/06/PKU_report_FINAL_v2_nomarks.pdf
[iii] Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017;12(1):162. Published 2017 Oct 12. doi:10.1186/s13023-017-0685-2.
[iv] Pitt JJ. Newborn screening. Clin Biochem Rev. 2010;31:57–68. Last accessed April 2019
[v] Al Hafid N, Christodoulou J. Phenylketonuria: a review of current and future treatments. Transl Pediatr. 2015;4(4):304–317. doi:10.3978/j.issn.2224-4336.2015.10.07
[vi] Blau et Al. Management of phenylketonuria in Europe: Survey results from 19 countries. Molecular Genetics and Metabolism 99 (2010) 109–115
[vii] Ford, S. et Al. Living with Phenylketonuria: Lessons from the PKU community. Molecular Genetics and Metabolism Report. 2018
[viii] Bilder DA et Al. Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria. Dev Neuropsychol. 2016 May-Jun;41(4):245-260.
[ix] NORD. 2019. Phenylketonuria. Available at: https://rarediseases.org/rare-diseases/phenylketonuria/. Last accessed April 2019
[x] Berry et Al. Newborn screening 50 years later: access issues faced by adults with PKU. Genetics in Medicine volume 15, pages591–599 (2013)
PhD research study: Quality of life and social support for adults living with EB and other rare skin conditions
Navigating Quality of Life and Social Support
Sondra Butterworth began her working life as a general nurse. During a career break to have her two children, she decided to study for a degree in Psychology and went on to gain a Master's degree in Psychology at Manchester Metropolitan University. It was during that time she gained an interest in Community Psychology and the empowerment of people living with disabilities.
Sondra is currently a Health and Social Care PhD student at the University of Chester UK and works for the charity DEBRA UK. This is where Sondra became passionate about the social support and quality of life impact on people affected by Epidermolysis Bullosa (EB), going on to produce the literature review along with Dr. Kate Martin, Consultant Clinical Psychologist EB Service and Dermatology, Solihull Hospital, supported by DEBRA UK. (Read the abstract below.)
The next stage of the research includes an on-line survey which is aimed at adults living with EB and other rare genetic skin conditions.
Taking part in the survey
Quality of life and social support
About World PI Week
World PI Week is a global movement to raise awareness of primary immunodeficiency and related challenges; promote quality of life for people with primary immunodeficiency, early diagnosis, availability and access to treatment and care worldwide; and stimulate communication and advocacy around primary immunodeficiency.
Primary immunodeficiencies are rare diseases which occur when a person’s immune system is absent or does not function properly. When a defect in the immune system is inherited (carried through the genes), it is called primary immunodeficiency. There are over 320 forms of Primary Immunodeficiency (PI or PID), ranging widely in severity.
Primary Immunodeficiency often presents in the form of “common” infections, sometimes leading physicians to treat the infections while missing the underlying cause, allowing the infections to reoccur, and leaving the patient vulnerable to vital organ damage, physical disability, and even death.
For more information, please visit www.worldpiweek.org, follow us on Twitter @WorldPIWeek.
Bénédicte Faure, campaign manager: email@example.com
EspeRare enters into partnership with Dermelix Biotherapeutics to develop DMX-101, an in utero treatment for X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
- DMX-101 has the potential to become the first ever in utero administered drug to correct a genetic disease before birth
- EspeRare and Dermelix aim to initiate the pivotal trial in Europe and then in the US in the second half of 2019
- Both partners have signed an Ethics and Social Responsibility Charter under which they commit to continuously engage with the patient community during the development of the therapy
Geneva, Switzerland – 2 April, 2019 – EspeRare, a not-for-profit organization dedicated to accelerating the development of rare diseases treatments, today announced that it has entered into an agreement with Dermelix Biotherapeutics for the co-development of its lead programme, DMX-101. DMX-101 is a novel in utero protein replacement therapy for the treatment of X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED), a rare pediatric genetic disease.
Under the terms of the agreement, EspeRare will sponsor the development of DMX-101 (previously ER-004) in Europe, where it was accepted under the EMA’s PRIME (Priority Medicines) scheme and benefits from Orphan Drug Designation. Dermelix will sponsor the development of DMX-101 outside of Europe and will be responsible for its commercialization worldwide.
XLHED is a rare genetic disorder affecting ectodermal structures including sweat glands, respiratory glands, skin, hair and teeth. Clinical manifestations of XLHED are severe and can include life-threatening episodes of hyperthermia, heat intolerance, and an increased risk of serious respiratory tract infections. There are currently no approved therapies for treatment of XLHED and the current standard of care is only palliative.
DMX-101 is a protein replacement therapy designed as a substitute for endogenous EDA, a protein missing in XLHED. It is administered during late foetal development through a single-course treatment delivered into the amniotic fluid. This approach has already demonstrated significant benefits in a prenatal study, the results of which were recently published in the New England Journal of Medicine1 and featured in Nature Medicine’s 2018 Research Highlights2.
In the second half of 2019, EspeRare and Dermelix anticipate the start of patient enrollment into a pivotal study for DMX-101, first in Europe and then in the US, with the aim of moving the treatment towards market approval. In the US, DMX-101 benefits from Orphan Drug Designation and Fast Track Designation by the FDA.
“Patients with rare diseases so often lack the treatment options they need. This partnership with Dermelix represents an amazing opportunity to bring an innovative therapy to patients and to potentially change their lives radically. Beyond XLHED, we are committed to paving the way for other prenatal treatments to correct genetic diseases before birth.”
Dr. Nick France, Chief Medical Officer of Dermelix, commented: “It is both tremendously exciting and humbling to be able to participate in such a groundbreaking program. The ability to correct a severe disease before birth represents a huge step forward in therapeutic paradigms. We look forward to a productive collaboration with EspeRare and working hard for families with XLHED.”
In line with EspeRare’s model and in order to reflect EspeRare and Dermelix’ common values and patient-centric approach, the agreement also includes an Ethics and Social Responsibility Charter under which both partners have committed to fully and transparently engage the patient community. Through a Patient Advisory Council, the partners will streamline information transfer in order to provide valuable inputs for the development of DMX-101.
- N Engl J Med 2018; 378: 1604-1610
- Nature Medicine 2018; 24: 702
XLHED is a severe, chronically debilitating and life-threatening rare disease affecting approximately 4/100,000 live male births every year. XLHED is caused by genetic mutations in the EDA gene, a gene that encodes for an important ectodermal developmental protein, EDA. The absence of functional EDA results in abnormal development of the skin, sweat glands, sebaceous glands, hair, oral cavity, and respiratory mucosal glands resulting in serious life-threatening clinical manifestations from birth including hyperthermia, craniofacial anomalies and recurrent respiratory infections that impair quality of life in patients and their families.
For more information, please visit https://bit.ly/2KbMqGa
EspeRare is a Swiss not-for-profit organization that is committed to improve the lives of children with life-threatening rare diseases. EspeRare addresses the unmet medical needs of these children by uncovering the potential of existing treatments. EspeRare’s innovative model combines pharmaceutical know-how with philanthropic, public and private investments to develop and bring to life these discontinued therapies. With its unique patient-centered approach to drug development, EspeRare engages the patient community at each step of the process, with the intent of giving children and their families fair access to these therapies and a new hope for the future. For more information, please visit https://esperare.org/en/node/13
DMX-101 is a fully humanized EDA molecule consisting of the human IgG1 Fc sequence linked to the human EDA TNF binding domain. Preclinically, DMX-101 has been shown to bind to the receptor EDAR resulting in activation of the NFϰB signaling pathway, which triggers the transcription of genes involved in the normal development of multiple tissue types. DMX-101 is the first and only treatment specifically targeting XLHED. Administered during the third trimester of pregnancy, it has the potential to become a “single course” treatment, significantly improving symptoms of the disease throughout patients’ lives. This approach has already demonstrated significant potential in in a case series of three patients treated in utero with DMX-101 during the third trimester of pregnancy. The treatment normalized sweat gland function and associated thermoregulation, and improvement in dentition and respiratory function were observed. These results were recently published in the New England Journal of Medicine1 and featured in Nature Medicine’s 2018 Research Highlights2.
For more information, please visit https://esperare.org/en/dmx-101
About Dermelix Biotherapeutics
Dermelix is a privately-held, clinical-stage biopharmaceutical company focused on the development of innovative therapies for rare and debilitating dermatologic conditions with high unmet medical need. For more information, please visit https://www.dermelix.com
For English-speaking and International Media:
Instinctif Partners for EspeRare
Sue Charles / Dr Christelle Kerouedan / Genevieve Wilson
T: +44 (0) 20 7457 2020
The march has been organised by a group of pioneering researchers and medics who have made a breakthrough discovery that the ‘patients were in fact right all along’. A recent paper published on PubMed set out the results from a 15 year research project, costing over one billion pounds, which concluded that at no time in history has civilisation experienced a pandemic of Munchhausen syndrome or Munchhausen by proxy (previously factitious disorder) – an illness in which a person fabricates illness for themselves or a dependent and puts them through unnecessary medical treatment. The study went on further to conclude that it found 99.87% of patients presenting in the consultation room were credible and educated individuals, who were highly informed and able to articulate their symptoms accurately.
The study states that these problem patients were in fact found to be affected by one or more of over 7,000 rare diseases which it estimated accounts for some 350 million patients worldwide.
Dr. A (who preferred to remain anonymous), told us:
“The results of this study are astounding. It turns out our patients were right all along. Fancy thank – who knew!”
The organisers hope to see millions take to the streets and are already setting their sights on planning the 2020 march. “With a century of attitude to overturn there is much work to do, but this study and march are an important first step. Next we will be recalling the following posters which are known to adorn many a GP waiting room walls – PLEASE DON’T CONFUSE YOUR GOOGLE SEARCH WITH MY MEDICAL DEGREE.
Instead they will be replaced with the following Medical Association approved poster.
I PROMISE NOT TO UNDERMINE YOUR LIFETIME OF LIVING WITH YOUR CONDITION BASED ON MY ONE HOUR MEDICAL SCHOOL LECTURE ON IT.
Doctors and patients alike all agree – these are exciting times!
Take the new Rare Barometer Voices survey on rare disease patients’ experience of treatments and make your voice heard
Eurodis, the non-governmental patient-driven alliance of patient organisations is asking people to share their experience of rare disease treatments via their new Rare Barometer Voices survey.
Is there a treatment for your rare disease? Are you able to access it when and where you need it? Has this treatment resulted in a positive or negative experience for you?
Through asking questions such as these we will be able to better measure and understand the unmet treatment needs of people living with a rare disease. The new global Rare Barometer Voices survey will generate facts and figures which can be used to advocate for positive change with regards to access to, research on and administration of treatments for the rare disease community
This global survey is open to anyone from any country in the world who is living with a rare disease, as well their family members and carers. The survey is available in 23 different languages and all responses are anonymous.
It takes 10 minutes to complete the survey online and the more people who respond and share their experiences, the more powerful our voice will be!
If you are not already registered to participate in the Rare Barometer Voices program, you will be asked to complete a short registration form before you begin the survey. The survey closes on 30 April.
How will the results of the survey be used?
The survey responses will be used to develop insights into the experience of people living with a rare disease in relation to treatments. We will be able to generate an overview of rare disease patients’ experience of treatments at a global level as well as breakdown the results by geography, disease group, gender and age.
The results will be shared with patient organisations, policy makers and the general public. The findings will be used by Eurodis in their advocacy work to drive real change for people living with rare diseases. The key insights will also be shared with all respondents via email and social media and the full report and associated infographic will be made available on the Rare Barometer Voices website.
Why Rare Barometer Voices?
Rare Barometer Voices is the EURORDIS-Rare Diseases Europe survey initiative that brings together over 8,000 rare disease patients, family members and carers who share their experiences and opinions on the issues that matter to the rare disease community. Rare Barometer Voices was created to systematically collect patients’ opinions on transversal topics and introduce them into the policy and decision-making process. The objective of the programme is to transform patients’ and families’ opinions and experiences into facts and figures that can be shared with a wider public and policymakers.
Eurodis would like to thank you in advance for your participation. For more information, visit Eurodis
The UK’s first drug trial for Rett Syndrome
After the warm welcome from Rick Thompson, CEO of Findacure, we heard from Reverse Rett and Rett UK. Rachael Bloom Stevenson, CEO of Reverse Rett talked about Reverse Rett’s involvement in the first UK clinical trial for Rett Syndrome in 2017, which was launched at King’s College Hospital in London under Professor Paramala Santosh. Becky Jenner, CEO of Rett UK and parent to Rosie, spoke about her daughter’s experience of participating on the trial and the benefits that they personally have experienced from the trial.
Repurposing nitisinone in alkaptonuria
Professor Lakshminarayan Ranganath, Director of the National Alkaptonuria Centre (NAC), is a consultant at the Royal Liverpool Hospital, he talked about repurposing nitisinone in alkaptonuria patients.
Alkaptonuria (AKU) is an iconic autosomal recessive condition, caused by a faulty enzyme (homogentisate dioxygenase) in the tyrosine degradation pathway that results in a build up of homogentisic acid (HGA) in the body. This affects multiple systems in the body including the spine, joints, heart, ligaments, eyes and kidneys.
Nitisinone has been used in a related disorder, hereditary tyrosinaemia 1, as the standard of care for more than 20 years. Data collected from the NAC shows a beneficial effect of nitisinone in AKU.
Pharnext on Pleotherapy
Pharnext is an advanced-clinical-stage biopharmaceutical company. Rodolphe Hajj, Chief Pharmacology Officer and Xavier Paoli, Chief Commercial Officer at Pharnext, gave a joint talk about Pleotherapy™, a platform that systemises the identification and development of new synergistic combinations of repositioned drugs for diseases with high unmet medical needs. These new therapeutic entities are called PLEODRUG™ and they are expected to feature high levels of efficacy and safety due to being formulated with new, optimal, lower doses of their individual components, and they target simultaneously several disease pathways.
We had the pleasure of hearing from Logan Williams, winner of The Student Voice essay competition. Logan is a final year medical student at The University of Auckland. The title of his essay Repurposing: a rare opportunity: a brief insight into how implicit bias towards biomedicine impacts the care received by patients with a rare illness. His essay focused on his experience of treating a five-year-old boy with worster drought syndrome and how he became inadvertently caught in the trap of focusing on the boy’s diagnosis rather than the patient.
After speaking to the boy’s mother, Logan searched to understand the origin of biases towards biomedicine, with himself and the medical system, believing it is imperative that patients and families are given a voice.
Dr Pan Pantziarka spoke about his work as part of ReDo (Repurposing Drug in Oncology) and an AMRC led repurposing round table group, which aimed to facilitate the use of off-patent repurposed medicines within the NHS.
Idebenone: how repurposing this drug is helping Duchenne muscular dystrophy
Catherine Lawrence, Senior Medical Advisor UK at Santhera and Janet Bloor, parent and Duchenne Advocate, and Vice Chair at RACC, jointly discussed advocacy for Duchenne, the development of the drug Idebenone and the subsequent clinical trial.
Duchenne muscular dystrophy is a rare genetic muscle wasting life-limiting disease. Santhera was the first pharmaceutical company to address the hugely unmet needs of older non-ambulatory boys, and has been trialling Idebenone, originally developed for Alzheimer’s, as a respiratory drug for Duchenne.
Janet talked about how her son (who is now 25) and has been on this trial for 18 months. Janet is a strong advocate of having a registry for your disease that is interconnected on a global scale.
A life with PNH: from isolation to treatment
The last speaker of the day was Suzanne Morris a PNH Patient Representative. She was diagnosed as a child in the 1970s when there was very little help or support. It was incredibly moving to here Suzanne speak of living her life in secret for decades. After her diagnosis and in the following years she talked of the difficulty of living with PNH in a time when there was a lot of prejudice in society against blood diseases. Suzanne also discussed the lack of focus on the mental side of conditions and how this is not taken in to consideration. This led to a discussion about compulsory counselling and the benefits that this could potentially give to patients and their families.
Suzanne featured in our RARE Blood issue read it here.
Rare Revolution Editor