Last month, the National Organization for Rare DisordersⓇ (NORD) broke previous records with its 2019 Rare Diseases & Orphan Products Breakthrough Summit, welcoming over 900 registrants to two days of unforgettable keynotes, powerful panels, breakout sessions and networking in Washington, DC.
The NORD Summit is the largest and most innovative multi-stakeholder event of its kind, drawing together participants from across the rare disease community—including patient advocacy groups, government, industry and academia—to discuss the most current and urgent topics related to rare diseases and orphan products. The 2019 theme focused on why “The Time is Now” to drive innovation, collaboration, advocacy and research. These topics included perspectives from a diverse group of thought leaders.
There is No Time Like the Present – Inspiration to Action
The 2019 Summit kicked off the morning of Monday, October 21 with a greeting from NORD’s President and CEO, Peter L. Saltonstall, followed by an emotional Patient/Caregiver Opening Address, “There is No Time Like the Present – Inspiration to Action.” Speakers Terry Jo Bichell and Karen Aiach are mothers and rare disease warriors whose stories illustrated how families impacted by rare diseases are helping to drive progress in research, an increased understanding of diseases and the development of treatments.
Keynote speeches were informative and inspiring, with speakers including CDER’s Associate Director for Strategic Initiatives, Theresa Mullin, PhD and FDA Acting Director Ned Sharpless, MD. Tuesday morning marked an impassioned keynote speech delivered by Health and Human Services Secretary Alex Azar, the highest ranking government official ever to speak at a NORD Summit.
“Effective treatments are often hard to come by, requiring years of expensive maintenance therapies. When successful therapies are developed, they’re not cheap. We need to ensure that Americans who suffer from rare diseases have ways to finance their care–while also making sure that our financing system can support innovation toward the cures we need,” said Secretary Azar.
Health and Human Services Secretary Alex Azar speaking at the NORD Summit on October 22, 2019 (Photo courtesy of National Organization for Rare Disorders)
Other highlights from the Summit included panels featuring key opinion leaders, an NIH conversation on why it is a unique moment for rare disease research, a town hall with the three FDA Center Directors and an interactive dialogue with FDA senior staff.
Rebecca was born weighing 6lbs 3oz and as far as I knew then everything was fine. I'd had no problems during pregnancy and she arrived on her due date. Yet, straight away she was sick after every feed, didn’t gain weight and she was classed as failure to thrive. At eight weeks old she had her first appointment with a paediatrician, who she saw regularly. Rebecca had all sorts of tests done for allergies, celiacs disease, and many other things, but nothing was found.
When she was a toddler we even saw a geneticist, but after many months nothing was detected and that was the end of that.
She spent the first few years of her life in and out of hospital every few weeks. Picking up every infection going, including numerous gastrointestinal bugs, which often led her to become dehydrated, and so she was back in hospital on a drip each time. I came to know the hospital so well and after one particularly long stint, felt like I was scared to bring her home, it felt much safer there under constant medical supervision. As the years passed and she started school, apart from a fractured elbow from a fall off a trampoline when she was four, several bouts of tonsillitis and a few other infections, things did seem to settle a bit.
However, it became apparent that she was much smaller than her peers and didn’t grow very much. Clothes and shoes lasted her for a really long time and her little sister, Olivia, started to overtake her in height and weight, with clothes and shoes being passed down to Rebecca from Olivia instead of the other way around.
Olivia thankfully doesn’t suffer from the syndrome but does carry the gene, there’s potentially a 1.4 million chance she’d meet a man with the same gene and a 1 in 4 chance they’d have a baby with this syndrome.
At this point Rebecca still had not been diagnosed.
Fast forward to 2012 when I was pregnant with Adam. At first everything seemed fine and he was a real wriggler but towards the last couple of months of the pregnancy I felt he wasn’t growing much, but when I expressed my concerns I was assured he’s measuring as he should be and everything was fine. In the last six weeks of pregnancy I had pre-eclampsia and they monitored me closely. A week before my due date I went in for monitoring and they told me my blood pressure was sky high and they admitted me. A short time after admission they took me to critical care as my baby was in distress and I had an emergency C-section, Adam wasn’t breathing. He was born at just 5lbs 4oz and just a few hours later the nurses took him for blood tests.
For another three years we spent so much time in and out of hospital, just like Rebecca, Adam picked up every infection and bug. He had severe chicken pox at just four months old and his doctors said they’d never seen such a severe case in a young baby. He was hospitalised again for four days. On another occasion he was so poorly he spent 10 weeks in a lethargic and sad state. His normal.
Adam's personality is and always has been so happy, always laughing giggling and generally just smiling, through every illness, but this time, for ten weeks he just sat on the couch or lay on my shoulder. He never smiled in all that time, no laughing no crawling, it was truly heartbreaking. I wasn’t sure I’d ever get my laughing boy back again. He did eventually come out of whatever it was and got back to his happy self, but he didn’t gain weight very well and is much smaller than other children his age. He was so thin you could see his ribs clearly even now if he has no top on. He had a rash when he was three which eventually led to his diagnosis. It didn’t itch or bother him but it stayed for several weeks and it was only when a colleague of the geneticist mentioned it looked like a rash associated with Rothman-Thompson syndrome, that they delved into it further. As it turns out that syndrome overlapped with two others, one being RAPADILINO Syndrome!
With Adam's diagnosis in August 2015, Rebecca was then tested a few weeks later and was also diagnosed with RAPADILINO.
Belgium and my two children here in the UK as well as one other little girl in the UK. It appears that most cases can differ quite a bit from each other. I sadly know that many cases have had to deal with cancer and amputation of limbs, in particular the leg. It’s the worst part of this condition although the constant pain and discomfort is also heartbreaking to watch in your child. Pain relief helps to a point, but never seems to take it away completely.
Adam and Rebecca today
For my son, who is now seven, he suffers with pain in his legs but thankfully not all of the time. He has had two operations on his thumbs as he was born with both thumbs with no knuckles or muscle. He can now use them but not very well and they’re not very strong. He still largely uses his two main fingers to write and do buttons etc.
My daughter Rebecca turned 15 on 6 September, over the last few years she has suffered a broken coccyx bone and has been treated for a fractured knee, although later on this became apparent that it’s the way her knee joint has grown and it’s not actually fractured. Four years ago she had another episode of what we thought was a fractured knee and walked with crutches for about a month having a lot of pain in her knee and leg. This settled down and she was OK for a while apart from intermittent pain in her legs.
Ten months ago she started to suffer very badly again with her knees and legs to the point she couldn’t walk and was given crutches and very strong painkillers by the hospital. Unfortunately, this doesn’t appear to be an episode and doctors now believe this is the way it’s going to be for her permanently. She’s had to give up her dream of dancing and playing football and she’s suffered in other, more personal ways too.
It has affected her massively and she’s had a lot of time off school. She has fallen a few times when her knee has given way and she has to be physically picked up and helped back to the couch, she is distraught when this happens and questions us, asking if this is it for her now, and will she never be able to go back to doing normal things again? She puts on a good front for other people because she feels embarrassed and self conscious and isn’t good at showing people, even family, how she’s actually feeling and how much pain she’s in. Sometimes she gets really scared as she gets pains randomly, and not always in the same place. The pain is either in the back of her knees or legs but in recent weeks her arms have started to ache a lot and it worries her all the time. She’s on a lot of painkillers three to four times a day, every single day!
The chances are we will go through something similar in the future with Adam but at least we’ll know roughly what to expect.
I would like to be able to raise awareness of this syndrome. I am still hoping to find a medical professional I can speak with that has had direct dealings with this syndrome. Our consultant is wonderful, both he and the nurse are really supportive and always try to put our minds at rest when we see or speak to them, but the constant worry and fear is always there.
For further information
Danielle Drachmann talks to RARE Revolution about the condition idiopathic ketotic hypoglycemia, (the most frequent cause of hypoglycemia in children between one and five years of age) hypoglycemia can be a life-threatening event. This is a condition that she and her two children have, which has led to Danielle setting up the website Hypomom, a platform she uses to share stories from a family with hypoglycemia and offering tips and advice about living with this
But just like other rare disease parents out there, no one could have ever prepared me for what life had in store. I’d like to present to you two very different perspectives on motherhood. Before, and after the realisation that our ball of sunshine was a particularly special one!
My baby, Noah, had just had a rough night with lots of screaming and unease before he went to sleep, well what I thought was sleeping. I remember the student nurse standing with her blood sugar device, staring terrified at those two digits on the screen, her face turning ghoulishly white, before she proceeded to push the emergency button, and then she pulled my baby boy from my arms, sprinting out of the ward as if chased by a lion.
I flew up from my bed and rushed after the student nurse following her further into the hospital. In that moment I ceased to be a child, and my life as an adult began, forced by circumstance and necessity, into a journey I never thought I had the strength to live through.
Neonatal intensive care unit
Weeks later, after I had accepted Noah did suffer from a blood glucose related rare condition, I found myself in what felt like a different planet, attending the hospital ward with all the other very sick kids. I was juggling foreign words, hypoglycemia terms, the creaking sounds of breast pumps, alarms, crying parents and very sick newborns and glucose drops, while facing an army of doctors and nurses at what became known to me as the NICU.
I forgot it was difficult. I forgot I didn’t knew how to be a parent. I forgot I had to learn to navigate this new planet, with their foreign language and their hierarchical culture from scratch. I forgot I had had another life just a few days before I crashed down to this strange place, where I four years later, I find myself well-established in what is in fact a great life for me and my rare disease children.
The years of being a rare-disease-parent has taught me my biggest superpower: Trusting my gut and reaching for the right mentors and specialists. These people have all been willing to teach me everything Google and the library couldn’t, arming me with a special needs parents strongest weapon in the fight of protecting your child: Knowledge.
How I managed to let go
After the early years of childhood with my wonderful hypo-kids, one day I found myself sitting with Noah who had turned into this little human being with an actual personality, old enough to go to kindergarten and begin his first day in his life as a big boy.
Although every inch of my body wanted to embrace my children forever in our safe concrete bubble made from love, fear and delicious fat baby cheeks - the reality knocked on the door: Noah was starting in kindergarten, and he really needed it!
And to be honest, I did too. I needed to talk to grown-ups for a change, after singing “The Wheels On The Bus” for the 50th time in a day for four years, while also being tasked with handling everyday life, ambulances and seizures. Not an ideal cocktail for any new parent, and especially not for four years without breaks.
I faced my fears and wrote down what scared me the most. I came up with the following:
1. What if the staff forgets what to do, by the different blood glucose values?
2. What if the staff is so uncomfortable taking responsibility for him, they end up excluding him in order to protect him?
3. What if one of the kids ends up in a seizure, and they forget important info to the paramedics?
I mustered up all the courage in my body, picked up Noah and went to kindergarten - ready to tell them about my beloved child, who unfortunately came with a rare disease and special needs. We sat down, while Noah investigated the playground with all the other kids. The last thing I wanted was for my child to live a Dear Evan Hansen like reality, caged out from the rest of his peers.
What I witnessed in my son’s eyes when he was staring out into the playground was anything but frightful though. He was so excited about this place, new stuff and new kids. His excitement melted my heart, but I was also terrified of how much adrenaline and physical activity would be in store for him, so I was also fearful that it might trigger an incident.
After 20 minutes of explaining our situation and requirements for Noah, to the member of staff at his kindergarten, I drew in a deep breath, waiting for their response. After giving me an awkward glance, the kindergarten staffer noted the following: “So, he could end up brain damaged or worse in our custody, if we don’t discover he is in hypoglycemia?” Well, yes. That is in fact the case, and why I lay sleepless at night.
2 minutes later Noah ended up in hypoglycemia after an hour on the playground. My worst fear realised.
After stabilising him with juice and bread and having left the kindergarten, I cried. The staff had been terrified. And so was I. I considered the situation:
How would they ever be able to remember everything I told them of my child needs? To be honest, I myself have difficulty remembering everything when an emergency arises. I once I forgot Noah's social security number and could not remember if it was him or Savannah who reacted on Glucagon (and I’m their mother for goodness sake!).
If I can forget about life saving information about my kids emergency treatment, how could these strangers possibly be expected to?
The blood sugar guide
After that heart-wrecking day, I got an idea. I sat down and had a heart-to-heart conversation with my brother, Nick. He happens to be a classically trained graphic designer. After balling my eyes out for a while, I asked him if it was possible to produce some sort of easily accessible rare disease guide, to help kindergarten staffers navigate tough situations for special needs kids.
If I were to leave my kids in the hands of strangers, I needed the information in my head to be in a physical guide that I could trust anyone to follow. The first variation of the guide was sloppy, but with it, we ensured that we could provide the institutions a visual representation of how to react in any given scenario!
The guide helped us to move forward with new found enthusiasm. We feel like we’ve been able to give our two wonderful kids, the gift of childhood and the gift of friendship through their little buddies kindergarten and whatever lies ahead. We’re no longer terrified and on the verge of a nervous breakdown whenever we need the kids to be on their own, as long as we make sure the guide is handed over to whoever gets to look over our two wonderful balls of sunshine!
We feel safer than ever, and thanks to a combination of proper diet, a state of the art blood sugar guide and a loving online community, we can safely say that we’ve been on the journey of our lives, and each one of us in our little family are thankful for anywhere that fosters a safe space for parents of rare disease children.
Our hope is to open up this tool to include all rare disease children in the world. The guide is a tired but determined mom’s gift to anyone out there!
Thanks to years of work, we’ve finally acquired an understanding of how we should live a great life with ketotic hypoglycemia, which has been the underlying mission of Hypomom - to share everything we know, and show people out there, that you can live, and live well despite a rare diagnosis.
It took us a while to get here, but through many tests, trials and lots of lost nights of sleep, we’ve finally established a good understanding of our kids’ condition and special needs. We can’t quite claim victory on our own here though, as a close personal network of like-minded parents from all over the world have helped tremendously. Hypomom essentially brings an array of resources for all you rare disease parents out there, including:
Would you like a guide for your condition? You can contact us and let us know what you need in your guide, and we will make it happen here at Hypomom.com*
*This guide is a free service offered by Danielle at Hypomon.com
Patients with ultra-rare bone marrow disease set to benefit from £1.15m grant from LifeArc and The Aplastic Anaemia Trust
Supporting researchers from King’s College London and King’s College Hospital to test a personalised treatment approach for Aplastic Anaemia patients who have not responded to available therapies
LifeArc, a UK-based medical research charity, and the Aplastic Anaemia Trust (AAT) have jointly awarded a £1.15m research grant to King’s College London and King’s College Hospital to investigate the potential of a novel type of “personalised cellular therapy” to reverse the ultra-rare condition aplastic anaemia (AA). The results of this research could give new hope to people living with a severe, life-limiting form of this condition.
The grant will fund a clinical trial to investigate the safety and efficacy of using a patient’s own T-reg cells to restore the blood-making function of the bone marrow. This follows laboratory-based research from the team of scientists where T-reg cells from a patient’s own blood were collected, selected for activity and multiplied. In a test tube, these cells prevented the immune system from attacking the patient’s bone marrow stem cells.[i]
For patients with this ultra-rare disease, we’re looking for the first time at a personalised medicine approach where their own immune cells could be used to alter their disease.
Professor Ghulam Mufti, Department of Haematological Medicine at King’s College London and King’s College Hospital, and lead study investigator said: “For patients with this ultra-rare disease, we’re looking for the first time at a personalised medicine approach where their own immune cells could be used to alter their disease. In AA there is a reduction in the number of T-regs and most of the ones that the AA patients do have are non-functional. We’ve seen success in the laboratory by selecting and bolstering the number of functional T-reg cells. Now, with funding from LifeArc and the AAT, we can investigate the potential of this approach in treating AA patients who currently have very limited treatment options.”
AA is an ultra-rare life-threatening illness caused by the bone marrow failing to make enough of all three types of blood cells—red blood cells, white blood cells and platelets. Only around 100–150 people in UK are diagnosed per year, affecting all ages but most commonly people between the ages of 10 to 20 years old and those over the age of 60 years.
People with the illness are at greater risk of infections, bleeding, and can experience extreme fatigue, which leaves them unable to carry out simple daily tasks that most people take for granted. Around one in three patients with severe AA fail to respond to existing drug treatments and the other option — a bone marrow transplant – is reliant on finding a suitable donor, requires life-long treatment with immunosuppression therapy and is unsuccessful in one in three people.
LifeArc set up the Philanthropic fund to support translational research into rare diseases, where there is less interest from commercial organisations. Patients with AA can have limited treatment options; this opportunity with King’s College London, King’s College Hospital and the AAT has the potential to transform the lives of patients living with a severe form of the disease.
Dr Catriona Crombie, LifeArc’s Head of Philanthropic Fund explained why the charity had approved the funding: “LifeArc set up the Philanthropic fund to support translational research into rare diseases, where there is less interest from commercial organisations. Patients with AA can have limited treatment options; this opportunity with King’s College London, King’s College Hospital and the AAT has the potential to transform the lives of patients living with a severe form of the disease.”
The trial at King’s College London and King’s College Hospital will run for a duration of three years and aims to recruit nine patients. A blood sample of the patient’s T-reg cells will be extracted, purified and grown in the lab before being given back to the patient in a higher concentration. As patients with AA are more susceptible to infection, this personalised treatment approach is more likely to avoid the risk of severe infection and inflammation.
AA can severely impact a person’s quality of life. Through AAT’s close work with King’s College London and King’s College Hospital as a specialist centre of clinical care and research in AA, we identified the project with the most potential to directly benefit patients who are currently at a loss for solutions.
Grazina Berry, CEO of the AAT said: “AA can severely impact a person’s quality of life. Through AAT’s close work with King’s College London and King’s College Hospital as a specialist centre of clinical care and research in AA, we identified the project with the most potential to directly benefit patients who are currently at a loss for solutions. We are delighted to have partnered with LifeArc and King’s College London and King’s College Hospital to progress this ground-breaking work, which could potentially enable people living with severe AA to once again lead a normal life.”
About Aplastic Anaemia
Aplastic Anaemia (AA) is a rare and life-threatening illness caused by the bone marrow failing to make enough of all three types of blood cells - red blood cells, white blood cells and platelets. It is estimated that between 100 and 150 people will be diagnosed in UK alone every year. That is around 2 people for every 1,000,000 of population, making AA a very rare disease. In most cases of AA, the immune system attacks the bone marrow, thinking it is faulty. This makes the bone marrow function slow down, leading to the under-production of all types of blood cells.
The most common symptoms of AA are anaemia - caused by a lack of red blood cells - with the associated feeling of fatigue, shortness of breath, headaches and, occasionally, chest pains, and increased risk of infections caused by low white blood cells. Low platelets cause people to bleed easily. Being more susceptible to severe and life-threatening infection and bleeding complications makes AA a highly dangerous disease. Patients will visit hospital regularly to receive blood transfusions and treatments for infection; many will be admitted to hospital for weeks at a time while they receive treatment, and those who recover must take a lot of time regaining their strength, avoiding places where they could easily pick up infections.
There are currently two standard first-line treatments for AA: immune-suppressive therapy (IST), which uses medicines (antithymocyte globulin (ATG) and ciclosporin) to dampen down abnormal immune responses, or bone marrow stem cell transplantation, the only known curative AA treatment to date, but suitable only for a proportion of patients. A bone marrow transplant is an intense procedure that requires an immunological matched donor and may require lifelong immunosuppression therapy, which can lead to further debilitating side effects. Both bone marrow transplants and the combination of ATG and ciclosporin work in only around 2 in 3 of AA patients.
About the Aplastic Anaemia Trust
The Aplastic Anaemia Trust is the only charity in the UK dedicated to research into aplastic anaemia and allied rare bone marrow failures and supporting everyone affected nationally. We have built productive working partnerships with major research and treatment centres of excellence in England, providing us with direct access to world-class experts, state-of-the-art labs and excellent patient care. Access to this medical and scientific expertise puts us in a strong position to identify areas of need, raise funds for research, and engage with the expert community in the UK and internationally. Our vision is a world free from aplastic anaemia and allied rare bone marrow failures. Our mission is to enable vital research into the causes of aplastic anaemia and other rare bone marrow failures that ultimately leads to finding a cure, and to support everyone affected by them, so they can lead healthy and fulfilling lives.
Our strategic objectives are
LifeArc is a self-funded medical research charity. Our mission is to advance translation of early science into health care treatments or diagnostics that can be taken through to full development and made available to patients. We have been doing this for more than 25 years and our work has resulted in a diagnostic for antibiotic resistance and four licensed medicines.
Our success allows us to explore new approaches to stimulate and fund translation. We have our own drug discovery and diagnostics development facilities, supported by experts in technology transfer and intellectual property who also provide services to other organisations. Our model is built on collaboration, and we partner with a broad range of groups including medical research charities, research organisations, industry and academic scientists. We are motivated by patient need and scientific opportunity.
Two funds help us to invest in external projects for the benefit of patients: our Philanthropic Fund provides grants to support medical research projects focused on the translation of rare diseases research and our Seed Fund is aimed at start-up companies focussed on developing new therapeutics and biological modalities.
Find out more about our work on www.lifearc.org or follow us on LinkedIn or Twitter.
About King’s College London
King's College London is one of the top 10 UK universities in the world (QS World University Rankings, 2018/19) and among the oldest in England. King’s has more than 31,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).
Since our foundation, King’s students and staff have dedicated themselves in the service of society. King’s will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King’s strategic vision for the next 12 years to 2029, which will be the 200th anniversary of the founding of the university. World-changing ideas. Life-changing impact: https://www.kcl.ac.uk/news/headlines.aspx
About King’s College Hospital
King’s College Hospital is a leading national and international centre for the diagnosis and treatment of blood cancers. The hospital is home to the largest bone marrow transplant programme in the UK and performs more than 160 transplants a year. King’s College Hospital is also an international centre for research into and the treatment of myeloid leukaemias, lymphomas and myeloma, and have the first immune gene therapy programme for leukaemia approved by the Gene Therapy Advisory Committee (GTAC). It is the first hospital in the UK to treat adult lymphoma patients with CAR T therapy, and it has an active CAR programme in lymphoma, leukaemia and myeloma. It is also a centre of excellence for myelodysplasia and expertise in matched and unrelated transplants for the treatment of myelodysplastic syndrome (MDS).
The haemato-oncology service:
For more information about the haematology service at King’s College Hospital visit https://www.kch.nhs.uk/service/a-z/haemato-oncology
Rare Revolution Editor