Patients, researchers and clinicians unite to fight rare disorders
Jennie Ogden remembers the first time she heard ‘Spinal Muscular Atrophy.’ “I didn’t know what it was, but I knew the word atrophy was serious.”
Jennie’s daughter, Sophie Blair, was in hospital with a lung infection. Previously, they had been in for some tests because at age 15 months Sophie was not able to pull herself up, one of the key milestones for developing babies.
When Dr. Craig Campbell began to see Sophie, he found that her muscles were weak and not moving as they should. He is a Neurology Paediatrician at Children’s Hospital, London Health Sciences Centre (LHSC) and a researcher with Children’s Health Research Institute, a Lawson program.
Following a blood test, the results showed Sophie had Spinal Muscular Atrophy (SMA).
“No one in our families had this condition – no one had even heard of SMA before,” says Jennie.
Jennie Ogden shares a special connection with her daughter, Sophie Blair. Sophie has a rare disease called Spinal Muscular Atrophy, which affects control of muscle movement.
SMA is a rare genetic disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells, called motor neurons, which travel between the brainstem, spinal cord and muscles.
This leads to weakness and wasting (atrophy) of muscles used for activities such as crawling, walking, sitting up and controlling head movement. In severe cases of SMA, the muscles used for breathing and swallowing are affected.
There are four main types of SMA. Type 1 is the most severe and symptoms start early on in an infant’s life. Those with Type 2 and 3 SMA experience weakness later in infancy or childhood and some may be able to sit or walk. The fourth type is rare and usually surfaces in adulthood.
“Without a cure or effective treatment, a diagnosis of SMA is often devastating for a family. For babies with Type 1 SMA, the life expectancy is only one or two years,” says Dr. Campbell. “Type 2 and 3 SMA patients often live into adulthood, but they become progressively weaker. They often have limited use of their arms and legs, and many are not able to eat without a feeding tube.”
“All we can do is try and stay one step ahead: treat symptoms, prevent problems and manage any pain,” explains Dr. Campbell.
Recessive genetic disorder: SMA is caused by a recessive genetic disorder. Children who are affected have inherited two copies of the mutated gene, one copy from each parent.
1 in 6,000 babies: It is a relatively common “rare disorder” with approximately 1 in 6,000 babies born affected, and about 1 in 40 people are genetic carriers.
More than any other genetic disease: The debilitating and progressive condition kills more infants than any other genetic disease.
Jennie feels lucky that Sophie has been very healthy for someone with Type 2 SMA. “She can sleep without ventilation assistance and has no curvature of the spine. But she’s lost muscle mass over time and we’ve seen changes in her body shape as she grows.”
The focus has been on keeping life as normal as possible. Despite not being able to move around much on her own, Sophie is a happy girl. “She’s quiet but sassy. Always my little partner in crime,” shares Jennie. Her favourite activities are singing, building doll houses and being outside.
Now that Sophie is six years old, she is in grade one at school. Math is her favourite subject. “She’s able to participate fully in class with the help of an education assistant, even in gym class thanks to special accommodations,” says Jennie. “Sometimes the other kids forget it’s hard for her to keep up though and this can hurt her feelings.”
Two years ago, Dr. Campbell told Jennie about clinical trials for a newly developed drug that may change the future for children and families living with SMA.
After participating in a clinical trial for a new drug treating Spinal Muscular Atrophy, Sophie, pictured here with Dr. Craig Campbell, can move in ways she couldn’t before.
Nusinersen, marketed as SPINRAZA, is the first treatment shown to improve motor function and reduce weakness for those with SMA. The biopharmaceutical company Ionis developed the compounds in the drug and partnered with Biogen to lead multinational clinical trials.
Lawson became involved in the phase 3 trial, a randomized control study, with London as one of only four clinical trial sites in Canada.
Sophie was among the first enrolled in the trial. “We understood there weren’t a lot of reported side effects, but there was a chance Sophie may not actually receive the treatment,” remembers Jennie. “Even if nothing changed for her, we knew that this was still a chance to help other families.”
With a strong safety profile and evidence showing that Nusinersen not only helped to avoid medical complications but actually improved skills, the children in the trial were moved to open label extension studies – they all received the drug. Additional patients with Type 1 SMA were also quickly moved onto treatment through a Special Access Program.
“Sophie didn’t have the lung infections she would usually develop in the winter,” says Jennie. “Her muscle mass stopped declining and she’s started to bulk up. She is now able to lift her hands above her head.”
“One of the most exciting changes was that Sophie can now shuffle on her bum,” adds Jennie. “We were used to staying in place wherever she was. One day, she scooted under a table, giggling and hiding. She has never been able to move like that on her own.”
PHASE I: Is it safe?
The first time the treatment or intervention is tested in people.
Safety and side effects of different doses are evaluated.
PHASE II: Does it do what it’s supposed to?
The effects (good and bad) of the treatment or intervention are found.
PHASE III: How does it compare?
The new treatment is compared to the standard treatment and safety for use is confirmed.
Most are randomized controlled trials with eligible participants assigned to either receive or not receive a treatment.
PHASE IV: What happens long-term?
This phase is carried out after the treatment has been approved for use.
The treatment may be compared to a competitor; its use may be explored with other patient groups; or, further side effects may be studied.
“We hope to follow the children on the study long term to systematically measure the benefits of treatment over time,” says Dr. Campbell. “It’s my hope that the drug can be made widely available in Canada to those families who need it.”
The paediatric neuromuscular clinic at Children’s Hospital, LHSC, follows about 20 children with SMA. The dedicated team of clinical and research staff work together to care for children with severe neuromuscular disorders and offer research opportunities.
“Clinical research fills the gap between the lab and the prescription pad when it comes to new treatment. There needs to be a vision and process in place – we’ve worked hard to become experts in clinical trials. And it’s the partnership between patients, families, clinicians, scientists and industry that will most successfully address the unique needs of those being treated for a rare disease.”
The team is committed to making the experience of participating in a clinical trial as stress free as possible for families, and regularly informs this community of new opportunities.
He notes that there is a very efficient health research system in London that supports development and clinical trials, giving patients in this region the first opportunity to participate.
Dr. Craig Campbell hopes to follow Sophie and the other children taking part in the study long term to systematically measure the benefits of treatment over time.
“Based on the care we received and opportunity to participate in research, we’ve decided to stay in London rather than move elsewhere. We truly have one of the best hospitals in the country,” says Jennie.
She is trying to keep her hopes for Sophie humble. “My biggest concern is that we avoid having to use assistive devices for breathing.”
When she grows up, Sophie wants to be a wedding dress maker. For now, Sophie’s biggest goal is to be able to stand on her own.
Children’s Hospital at LHSC, in London, Ontario is a world-class hospital with the latest technology and the best specialists, scientists and health professionals in Canada. As a regional referral centre, they provide specialized paediatric inpatient and outpatient services to children in Southwestern Ontario from birth through to age 18 years
CHRI, a program of Lawson Health Research Institute, has a long and proud history of discovering ways to prevent and treat diseases affecting infants, children and youth, and to determine ways to promote happy, healthy lives. They conduct research of the highest international standards, optimizing the life-long health of children and youth.
Dr. Craig Campbell is a part of the Children’s Health Research Institute, a research program at Lawson and is an Associate Professor in the Departments of Paediatrics, Clinical Neurological Sciences and Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry at Western University.
The Pediatric Neuromuscular Research Group has been generously supported by funding from Dominos Pizza, the Singeris Family, Jesse’s Journey Foundation, Muscular Dystrophy Canada, Parent Project Muscular Dystrophy, Rare Disease Foundation, Children’s Health Research Institute, Canadian Institutes of Health Research, Sanofi Genzyme, PTC and Valerion.