BY JON REY-HASTIE
We recently wrote a letter supporting the extension of ataluren/translarna to people with DMD who are no longer ambulant (with no upper age limit). The letter also has relevance to other treatments being developed to treat Duchenne:
Losing the ability to walk is often considered the major milestone of Duchenne Muscular Dystrophy in terms of disease progression. In the past, clinical treatment, such as physiotherapy and orthoses, focused on preserving ambulation for as long as possible, and was considered to offer little value after a child with DMD had gone off their feet. I experienced this personally with the use of prednisolone, when the clinical team decided in 1997 not to continue using steroids as soon as I lost ambulation. At the time, it was considered that the benefits did not outweigh the risks.
I’m pleased to say that clinical treatment has progressed significantly and there is a greater understanding of what can be done to delay disease progression in the later stages of disease, such as the use of steroids after loss of ambulation, ventilation, cardiac medication and continued physio and monitoring for upper limb function. This represents a greater awareness of the benefits of slowing down disease progression even after the loss of ambulation, which has translated into longer and better quality of life for people living with Duchenne.
Unfortunately, with many eligibility criteria focused on patient ambulation, it feels like those involved in developing and regulating new treatments are now in danger of falling into the same trap as DMD clinicians in the 80s and 90s.
From the perspective of those living with DMD, losing the ability to walk is just one of many milestones in the progression of Duchenne. It can sometimes be an arbitrary milestone, because the decision to stop walking is a somewhat personal decision based on the level of risk of falling and injury, as well as the level of fatigue, that children and their families are willing to tolerate. Even between two children with the same level of functional ability to walk, you could see one persevering at all costs, and one choosing to use a wheelchair earlier because it is easier.
For those of us living with DMD who have stopped walking, we often feel that walking is overrated! Using a wheelchair can be incredibly empowering and improves our quality of life, as we are suddenly more mobile, more independent and less exhausted. What is far more important to our quality of life is the ability to eat and drink without assistance, use the toilet by ourselves and breathe without a ventilator. It is delaying the loss of these functions that DMD treatments should be aiming at.
Any treatment that also offers the prospect of preserving cardiac and/or respiratory muscles can be crucial in preventing an early death. The progression of muscle loss in these areas typically starts well after ambulation has been lost and continues throughout the entire life of the person with DMD. Preserving cardiac function for longer means more years with our loved ones and more years contributing to the world.
Where disease progression occurs during childhood development, it can have a significant impact on how the child sees themselves in relation to their peers. The greater the disease progression, the more difference they perceive, and the harder they find it to “fit in”. Delaying this progression by even a few years gives the child an opportunity to develop the emotional resilience and maturity they need to deal with the more significant changes to their body and how they interact with the world.
At earlier stages of the disease, the impact of delaying progression can be hugely significant, for example preserving upper limb function can mean you can be independent for far longer. Preserving the ability to eat and drink and to take yourself to the toilet makes the difference between being able to go out for the day and having to stay at home because you don’t have anyone to help you. This could have a massive impact on a young person’s care needs, reducing the need for carers or parents to provide care.
In addition, delaying loss of upper limb function delays the psychological impact of becoming dependent on someone else for your care.
The loss of respiratory function often comes at a particularly difficult time for a young person with DMD, usually around the age they would enter higher education or employment. Many of the members of DMD Pathfinders recount experiences where they have had to postpone or even stop their education due to respiratory failure and associated infections. In some cases, they did not return to education, as a result missing a vital opportunity. Delaying the decline of respiratory function even a few years could allow them to complete their studies or enter employment, prior to developing life-threatening complications.
In later stages, muscle loss can affect chewing and swallowing, meaning that some adults require a feeding tube and are unable to safely eat. This loss is particularly difficult to adapt to and the psychological impact can be very negative. Delaying the progression of the disease in swallowing muscles can preserve healthy weight and allow adults with DMD to enjoy food and drink for longer.
As someone who has lived through almost total muscle loss, I can confidently assert that at any stage of the disease, slowing down progression would have been hugely beneficial to me. Even now, I have some very limited movement in my hands that enables me to drive my wheelchair and use a computer with ease, and this limited movement is incredibly valuable and improves my quality of life more than a non-disabled person might imagine. I know this will gradually be lost and I would be very eager to access treatments that could preserve this function for as long as possible.
In a general sense, any delay in disease progression means an adult with DMD is able to do more tasks independently for longer. The practical, emotional and psychological impacts of this cannot be underestimated. While many of us older adults have adapted and still manage to live a good life, I believe I speak for many when I say we desperately cling to the little remaining function we do have, and there are so many things we wish we could still do, from leaving the house without a carer to eating and swallowing, hugging our loved ones and signing our own name.