A woman who suffered years of misery because of a hereditary and life-threatening swelling disorder today told how a last-minute chance to take part in research at Addenbrooke’s changed her life.
Sian Harding, from Benfleet, Essex, says she has gone from injecting herself twice a week to keep excruciatingly painful symptoms at bay, to living a normal, happy life with her partner and everything to look forward to.
The 33-year-old said:
Taking part in this trial is the best thing I have ever done. It has 100 per cent altered my life – it’s a total game changer. I feel like a new person with a different, happier, personality.
Sian was born with hereditary angioedema (HAE), a rare and frequently misdiagnosed genetic condition that would go on to severely impact on her life.
Patients have a defect in the gene that controls a blood protein called C1 inhibitor and symptoms include episodes of oedema (swelling) in various parts of the body including the hands, feet, face and airway, which can lead to death by asphyxiation.
As a child Sian suffered classic abdominal pain and vomiting and became such a regular emergency case at Basildon Hospital, she was given automatic access to the children’s ward, rather than going via A&E.
None-the-less the cause of her condition was a mystery until at eight-years-old – having already had two exploratory operations for suspected appendicitis - she was accurately diagnosed by a doctor who had seen HAE before.
Acute treatment involved injections of symptom-controlling C1 inhibitor concentrate and then – to keep pace with Sian’s needs - intravenous infusions of the same via portacaths and Hickman lines twice a week. However, they came with their own catalogue of problems, including infections, more pain, and endless time off school.
Forever at her side was her mother, Ann, a hard-working businesswoman who was so determined to learn more about the condition and raise awareness, she eventually took over the chair of the fundraising charity haeuk.org (opens in a new tab)
By 17 Sian became the first sufferer taught to inject herself, which was timely because the unpredictable swellings moved from her stomach to “just about anywhere else”, which included her hands and feet, making walking impossible.
Like her mother, Sian’s gritty determination helped her succeed in business and despite previous bouts of illness she is now associate plant director with the plant division of a construction company she joined 17 years ago.
Following a recommendation Sian was referred to Addenbrooke’s, and in November was offered the last place on the second phase of an international clinical trial led in Cambridge by Consultant in clinical immunology and allergy, Dr Padmalal Gurugama.
Along with 27 other patients internationally, Sian underwent a single infusion of an investigational therapy, called NTLA-2002, which utilises in vivo CRISPR/Cas9 technology to target the KLKB1 gene, which is responsible for producing plasma prekallikrein. By editing this gene, the therapy reduces the levels of total plasma kallikrein and hence bradykinin that makes her blood vessels leaky, effectively preventing swelling attacks.
The results, which build on phase one trial involving 10 patients, have been so successful in Cambridge University Hospital, at Amsterdam University Medical Centre and the University of Auckland, they have just been published in the New England Journal of Medicine and will be presented at the American College of Allergy, Asthma & immunology’s annual congress.
Sian, who lives with fiancé Tommy, said:
As a child it was like someone grabbing my insides and twisting them and as I got older the swelling moved to just about anywhere – and especially my hands, legs and feet. I got used to injecting just about everywhere – at work, in the car, and even on a plane.
Going on holiday was a nightmare and involved carrying an extra suitcase of all my medical supplies. The anxiety of worrying about getting sick while away meant it was hardly worth going.
Sian added:
By contrast, this year we had a three week road trip to Spain, which was simply bliss. For the first time I wasn’t going to bed having to worry about waking with an attack.
Until is all taken away, you don’t realise what a burden living with the condition is. For the first time I’m able to dare consider what it might be like to have children and be well enough to look after them.
Dr Gurugama said he was “delighted” for Sian and described phase two of the trial as another “fantastic team effort” by clinicians around the world, and their patients. He added:
The results from phase two convincingly build on those from phase one, and offer real hope to patients suffering from a condition that until now had very few treatment options. It is absolutely vital for patients, and those clinicians who care for them, that this game-changing work continues.
Danny Cohn, internist at Amsterdam UMC and first author of the study said:
For many decades, patients with HAE were faced with a very limited number of treatment options to control angioedema attacks. The prospect of a potential, functional cure following a single-time treatment is overwhelming both for patients and physicians.
Dr Hilary Longhurst, an honorary senior lecturer at the University of Auckland said:
Kallikrein acts as messenger that triggers swelling and in patients with HAE, this protein is basically let loose. The fact that we can reduce its presence tells us that we're on the right track.
The trial has the support of American sponsor, Intellia, and will continue as the CRISPR-Cas9 therapy NTLA-2002 moves into the third phase of its clinical development.
Read more on the first phase of this research here
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