Facing the Future contributed by Sam Alexandra Rose

FACING THE FUTURE WITH A RARE DISEASE

CONTRIBUTED BY SAM ALEXANDRA ROSE

Photograph: Ross Sneddon, Unsplash

Sam Alexandra Rose 34-year-old Sam is a writer and blogger. Alongside this she is also the head of content for a digital agency and a PhD student. For her PhD she is researching how creative writing can have emotional and mental health benefits for people who are learning to live with the after affects of their cancer diagnosis and treatment. She knows this only too well, as she lives with CMMRD (Constitutional Mismatch Repair Deficiency Syndrome), a rare genetic condition that only one in a million people have. CMMRD increases a person’s risk of getting certain cancers and she is a three times cancer survivor, although each time has changed her life. Living with the constant shadow of cancer and the yearly barrage of tests she needs can be very difficult to deal with, taking a toll on her mental health.

Two months ago, my partner and I were getting ready for a two-week trip to Florida when I got the annual call from my local hospital’s endoscopy department. “We’re calling to book you in for your gastroscopy and capsule endoscopy. Can you come in next Wednesday?” I couldn’t – that was the day I was heading to the airport. “We’ll have to leave it for now,” the man on the phone said after I explained. That was two months ago and unless I missed a call while I was on holiday, they haven’t called back yet. At the time of writing, I’m going on holiday again next weekend. Friday to Monday, I’ll be in Elveden Forest Center Parcs with my partner. I have promised myself that once we’ve enjoyed that weekend, I will call the hospital and chase not only the gastroscopy and capsule endoscopy appointment, but also the six-monthly appointment with my consultant that has failed to turn up, as well as the post-surgery CT scan, the flexible sigmoidoscopy I’m due, and maybe even the results of the brain MRI I had three months ago.

It’s really hard to have to chase for something you don’t even want.

In fact, the first lockdowns during covid brought some relief because all of my appointments were delayed. For months, I wasn’t called by medical professionals needing to book me in for annual scans. I suppose I should have been worried, but instead I was glad. Two years later I’m waiting on annual tests again, and as a person living with CMMRD who would very much like to not have to deal with a fourth cancer diagnosis, I need to stay on top of getting myself checked. I don’t want to; I have to. But at least let me enjoy my weekend away first. I have to deal with this condition for my entire life, so for as much as I can, I want to do it on my terms.

At least let me enjoy my weekend away first. I have to deal with this condition for my entire life, so for as much as I can, I want to do it on my terms.

Sam shared photographs of her holiday memories on trips to Florida & Wales

To understand what constitutional mismatch repair deficiency (CMMRD) is, you first need to know what Lynch syndrome is. Lynch syndrome is a genetic condition that makes it more likely for a person to get certain types of cancer. It’s an inherited condition that affects genes called mismatch repair genes. When cells grow and divide, they sometimes make mistakes, which mismatch repair genes are supposed to correct so that the cells don’t become cancerous. In Lynch syndrome, these genes can be abnormal or have a “mutation” so they don’t work as they should – hence the increased likelihood of cancer developing. Each person has two copies of each gene, with one inherited from each parent. If one parent has Lynch syndrome, the child might inherit their “good” gene or their “bad” gene, and having the “bad” gene means they have Lynch syndrome too. Bowel cancer is the biggest risk for people with Lynch syndrome, but it can also increase the risk of gynaecological, pancreatic, prostate and brain cancer, depending on which specific genes are affected.

CMMRD then, is basically double Lynch syndrome. It’s what happens when both parents have Lynch syndrome and the child – in this case, me – inherits both faulty genes. My mother has one good copy of the gene and one bad copy, and so does my father. I could have inherited both of their good genes and not have Lynch syndrome at all, like my sister did, or I could have inherited one of their good genes and one of their bad genes and had Lynch syndrome. Instead, I inherited both bad genes and this is called CMMRD. We believe my brother, who died when I was a baby, also had either Lynch syndrome or CMMRD.

I’ve consequently had cancer three times – bowel cancer at the age of 22, followed by uterine cancer and duodenal cancer both at the age of 30. Talk about bad luck. But on the other hand, I am also lucky. Most people with CMMRD get cancer before the age of 18, with the average age being just 7.5 years old. There is a one in a million chance of having CMMRD – I am literally one in a million, and at the age of 34, I’m beating all of the odds.

There is a one in a million chance of having CMMRD – I am literally one in a million, and at the age of 34, I’m beating all of the odds.

Imagery courtesy of Sam Alexandra Rose unless stated otherwise

But the emotional toll of CMMRD is tough. For years I described myself as having Lynch syndrome. Even when I wrote my memoir I didn’t mention CMMRD once. I couldn’t bring myself to look it in the eye – if Lynch syndrome increases a person’s cancer risk greatly, what does CMMRD mean for me? How many more times will I get cancer? Will a brain tumour be next, like my brother had?

Because my risk is so great, every year I have a gastroscopy to look in my stomach, a capsule endoscopy for my bowel, and more recently, a brain MRI and a full body scan. I also have a flexible sigmoidoscopy, which is like a colonoscopy, every two years to look at the internal pouch that was formed after my ileostomy reversal. I’ve had my bowel removed and a temporary stoma formed. I’ve had Whipple surgery to remove my duodenum, gall bladder, bile duct and the head of my pancreas. I’ve had a full hysterectomy with my ovaries removed and now I can’t have children. Not only do I fear for the future, but I can also be hit with sadness about everything that has happened already. Sometimes all of this is very quiet background noise in my head. When the time comes for another test or scan, the background noise becomes very loud. But whatever volume it’s at, it never completely goes away.

It’s hard to think about the future with that background noise going on, but I try to do it anyway. If my partner and I get married, I know there will be appointments to plan it around. They pop up like roadblocks – when I try to visualise the future, it’s a road to whatever good thing we’re looking forward to, and if the event is a few months away, there is probably an obstacle in the form of an appointment first. It’s always a case of waiting for that appointment to be dealt with before I can properly look forward to the event. And then sometimes, it feels like the only excitement that happens, or the only good news, is negative test results. When I’m excited, it’s often not because of the presence of good things, but the absence of bad things. I’ve had a few scares where more tests have been ordered after something has shown up on a scan but turned out to be nothing. I know after a test I will either feel a horrible fear in my stomach, or a wave of relief I can take comfort in for days.

Despite dealing with CMMRD and feeling sad about the past and worried about a future littered with medical tests, I’ve done a lot. I’ve travelled a lot. I’m even in the middle of doing a PhD on my condition. Yes, it is scary to plan for the future, but I keep trying to fill up my life with good things and hoping I get to complete all of them.

Written by Sam Alexandra Rose

FIND OUT MORE • Take a look at Sam’s website & blog here • Read Sam's memoir here

HOPE for RARE

Caroline photographed by Julien Herger

Caroline Kant is a neurobiologist by training, with degrees in molecular biology, design and product development.

Her involvement across many disciplines, from the sciences to the arts, has given her the ability to work in innovative and exciting ways within the world of pharmaceutical research. Having spent six years in leadership roles at the pharmaceutical company Merck Serono life took Caroline in an unexpected direction. “Ten years ago, along with my co-founders Béatrice Greco and Florence Porte-Thomé, we had the opportunity to create EspeRare when we were working for Merck Serono and they had anounced the closure of the Geneva Headquarters." Caroline and her co-founders used the Merck Serono Entrepreneur Partnership Program to explore drug repositioning for rare diseases, and were granted initial funding of €2.8 million. In addition, Merck Serono transferred the rights to Rimeporide to them, a compound that had been initially developed for heart failure and that they believed could be successfully repositioned for treatment for Duchenne Muscular Dystrophy (DMD). Using this incredible opportunity as a starting point the EspeRare Foundation was set up as a not-for-profit organisation in 2013.

Sometimes in LIFE, it's about BEING at the wrong place or the RIGHT place, depending on how YOU look at it at the TIME.”

CAROLINE KANT

Carson was photographed by Ceridwen Hughes for Same but Different's Rare Aware project. Carson has Duchenne Muscular Dystrophy, click on the image to find out more.

Brief summary Rimeporide:

Duchenne Muscular Dystrophy (DMD) is a severe genetic paediatric disease that affects 1 in 3,500 boys worldwide. Patients affected by DMD have progressive weakness and loss of muscle function in their early childhood. Rimeporide is a selective NHE-1 inhibitor which could be used to address muscle degeneration and cardiomyopathy in DMD patients. EspeRare have generated compelling non-clinical and clinical data that validates the therapeutic potential of Rimeporide for those with Duchenne, and obtained Orphan Drug designations (Europe & the US). They have a proposed investigational plan ready to enter late clinical development, that aims at an accelerated market approval once a partner and/or funding has been secured. Caroline and her team had realised that the traditional commercial drug development model was not the most appropriate for developing, accelerating or prioritizing treatments for rare diseases.

“We started thinking about how an alternative business model could allow us to accelerate the development of treatment for rare diseases and put patient organisations at the centre of what we do. This is where we had the opportunity to establish the foundation."

They felt there was something missing in terms of how the development of these therapeutic opportunities could be funded, whilst also ensuring that the resources within the pharmaceutical industry were fully applied. Moreover, they identified that there is an important need for cooperation and coordination between the medical experts in rare diseases, the academic researchers and the patient community. "We mobilise philanthropic and public money to give a chance to treatments that are not initially of interest to the traditional pharmecuticals industry. Then we work to make them commercially viable. Our model, centred on patients and accessibility of treatmets is based on close collaboration between the various key stakeholders."

By developing infrastructures that span a breadth of interested parties, EspeRare is at the forefront of pioneering a new model of collaborative working within the framework of rare diseases. Working with patient organisations, EspeRare identify and choose which treatment they will seek to develop based on the therapeutic potential it may bring to the rare disease community. They also work to establish the commercial viability of these treatment, because this too is vital to ensure it could reach the stage of being distributed to patients.

Infographic from EspeRare detailing thier development model

Illustration courtesy of the EspeRare Foundation

“We are not the disease or patient group expert. We bring to our partners the drug development expertise in rare diseases."

As a not-for-profit, any profits they make are then reinvested into funding new projects in rare diseases and also into providing funding within the patient community.

"We try to have a continuum in terms of the alignment between medical experts, the research and the community. The patient community often initially funds the research to develop new treatments but since the drug development processes is so lengthy and costly, there's often a disconnect between giving back to the initial drivers of these innovations." As a not-for-profit drug developer, we try our best to have a risk sharing approach that basically has as an objective to advance life changing treatments in rare diseases, and to integrate ethical commitment in terms of accessibility to these treatments for patients. For us there is an ethical commitment that when you develop life changing innovations for patient communities, you endeavour to think about down the line. It should be accessible to patients that could benefit from it. I'm not pretending we're resolving the problem of excessive pricing and access of treatment in rare diseases. What we're trying to do is show that there can be alternative models that can become a game changer in driving forward accessibility and life changing treatments for rare diseases.”

Caroline photographed by Julien Herger

The first step towards creating change is often awareness, so a lived personal experience of the impact that rare disease can serve as the driving force behind many of those working within the rare disease community. Caroline’s twentyyear-old daughter Eva lives with a rare form of epilepsy, initally diagnosed aged seven, she finally received a genetic diagnosis at sixteen. “My daughter is my hero, and watching her fight her disability with courage and determination, she inspired me to also have the strength and live up to her courage. With my abilities and know how, I try to make a difference for these patients, and it's really her that gave me the courage try to do something differently.” Through having a child with a disability Caroline feels that she grew, not only as a mother, but as a human being within the world who could create change and hope. Hope for rare.

About the name:

When EspeRare was established the founders chose to create a truly meaningful and evocative name using three different European languages. In French ‘espoir’ means hope, whilst the Spanish version for hope is ‘espe’. In addition ‘esperar’ in Spanish means ‘to wait’, ‘to hold’ and ‘to hope’ which resonate with the lived reality of many within the rare disease world. Waiting for answers, holding their rare, hoping for an easier tomorrow. In replacing the ‘rar’ with the English ‘rare’ a literal translation of the name would be ‘Hope for Rare,’ which reflects the vision and mission of the foundation.

Putting patients at the centre, Connect in Pharma will bring together the key players in pharmaceutical and biopharmaceutical production in the heart of Europe’s pharma industry at their inaugural conference in Geneva in September 2022. The event will also host the premier of Same but Different’s latest photography exhibition, Days of Rare which features photos and video interviews with individuals who are affected by rare diseases. Connect in Pharma will also donate 5 Swiss francs per visitor to EspeRare Foundation, a notfor-profit organisation that identifies, develops and promotes access to life-changing treatments and technologies for patients affected by rare diseases. We talked to Caroline Kant, Executive Director of EspeRare about this exciting partnership;

“Our expertise is not about visually translating what we do, and we want to build awareness about rare disease and we really connected to the artistic sensitivity in your work. You bring the beauty and awareness around rare diseases. It's not only about suffering, it’s about strengths, and the beauty in the difference.”

Patients are at the core of advancing our treatments for rare diseases

Our unique collaborative model multiplies the impact of philanthropic investments and pharmaceutical knowhow to address the unmet needs of millions of patients with rare diseases

As a not-for-profit biotech, we identify, develop and promote the access to lifechanging therapies for patients affected by rare diseases

Leaving no one behind

EspeRare foundation Campus Biotech Innovation Park Avenue de Sécheron 15 1202 Geneva – Switzerland Email: foundation@esperare.org Website: www.esperare.org