This August is Spinal Muscular Atrophy (SMA) Awareness Month. It’s the perfect time to celebrate recent advances in treatment of this rare condition, which are inspiring hope for the 660–1320 children and adults living with SMA in the UK (1).
What is SMA?
Spinal muscular atrophy is a rare inherited muscle-wasting disease that is complex, debilitating and life-threatening. Symptoms include progressive muscle loss that consequently affects arm, hand, head and neck movement. This limits a person’s ability to walk, eat and ultimately, breathe (2,3).
SMA is the leading genetic cause of death in infants (2). Without treatment, children with the severest form of SMA rarely live to see their second birthday (1). However, others survive into adulthood and can live long, fulfilling lives (3).
The severity of symptoms varies both between and within the several different types of SMA, but each child and adult is affected differently by the disease (1). The most common form (accounting for 95% of cases (4)) is known as 5q SMA and there are four types within this form: type I develops in babies less than six months old; type II appears in infants who are 7–18 months old; type III develops after 18 months of age; and type IV begins in adulthood (3).
5q SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene (5). The damaged gene cannot make enough SMN protein, which is needed for healthy functioning motor neurons. The condition is recessive and inherited when a damaged gene is passed on from both parents. Non-5q SMA is a rarer form with a different genetic cause (5,6).
What treatment options are available?
SMA is not curable but treatments are emerging. Nusinersen▼, onasemnogene abeparvovec and risdiplam all show promise to treat 5q SMA. Nusinersen and onasemnogene abeparvovec both have a licence for their use in Europe. Risdiplam has submitted for approval of its European licence.
Nusinersen and risdiplam stimulate a poorly functioning backup gene, SMN2, to produce more of the essential protein that is missing. Both therapies are splicing modifiers.7-9
Onasemnogene abeparvovec is a gene therapy in which genetically-engineered viruses introduce a working version of the missing SMN1 gene back into cells (10).
Clinicians continue to pursue improved outcomes for those living with SMA.
SMA also affects adults
Although the majority (60%) of new SMA cases are of the most severe, infantile onset form of SMA (type I) (1), there has been increasing recognition of the condition in adults. While symptoms tend to be milder in adults with SMA, the condition is progressive, with muscle weakness, scoliosis (curvature of the spine) and muscle tremors increasing throughout life (11).
Nonetheless, treatments are now becoming available, holding real promise for clinically meaningful improvements in individuals who previously had no therapy options. Moreover, real-world data is beginning to emerge that supports the efficacy (12,13) and safety (13-16) of SMA treatment in adults.
The SMA community faces further challenges
Although genetic testing, screening for diagnosis, improvements in supportive care available and development of effective treatments have greatly advanced the management of SMA in recent years, patients aren’t always able to reap the full benefits. It’s a challenge to secure funding and the recent spread of COVID-19 has caused added pressure.
Clinicians have worked hard to ensure SMA patients can access the full benefits of novel diagnostics and treatments, early on. Early treatment following diagnosis can lead to better outcomes for patients irrelevant of which disease modifying therapy is chosen (13,17-20). It is essential therefore that patients have access to treatments at the earliest point in their disease course.
The SMA community will be key here. Patient advocacy groups (PAGs) and patient support groups have always been central to ensuring people living with SMA can benefit from advances in the field. Their determination to raise awareness and provide support has been invaluable in improving care and quality of life for those with the condition.
Helping to lead the charge
These considerable advances are matched by leaders in the SMA space with considerable enthusiasm.
I’m fortunate to have led Biogen’s efforts in SMA in the UK for the past three years, and it is an area I am very passionate about. I am privileged to able to be involved in a number of aspects, such as working with PAGs and clinicians, and recently negotiating with NICE and the NHS for reimbursement of nusinersen in the UK.
Having previously worked on reimbursement, I am switching my focus to support patient access to treatment and other advances. This means working at community level with PAGs and clinicians to make real change for patients with SMA. It is opportunities to make a difference like this that get me out of bed in the morning!
Written by Natalie Ghafoor, Commercial Director, Biogen.
1. SMA UK. What is spinal muscular atrophy. https://smauk.org.uk/what-is-spinal-muscular-atrophy
2. Committee for Medicinal Products for Human Use (CHMP). Assessment report – Spinraza, International non-proprietary name: nusinersen, 21 April 2017. Procedure No. EMEA/H/C/004312/0000.
3. NHS Choices. Spinal Muscular Atrophy. www.nhs.uk/conditions/spinal-muscular-atrophy-sma/
4. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015;51(2):157-167. doi:10.1002/mus.24497
5. Farrar MA, Kiernan MC. Neurotherapeutics. 2015; 12(2): 290–302.
6. Darras BT. Pediatr Clin North Am 2015; 62(3):743–66.
7. SPINRAZA Summary of Product Characteristics (SmPC). https://www.medicines.org.uk/emc/medicine/33559.
8. Hua Y et al. Genes Dev 2010; 24(15): 1634–44.
9. SMA UK. Treatments and Research: Risdiplam. https://smauk.org.uk/risdiplam
10. SMA UK. Treatments and Research: Zolgensma. https://smauk.org.uk/how-does-zolgensma-work
11. SMA News Today. SMA life expectancy and disease onset. https://smanewstoday.com/sma-life-expectancy/#:~:text=SMA%20Type%204%20(adult%2Donset,and%20muscle%20tremors%20and%20twitching
12. Osmanovic A, et al. J Neurol 2020; 267(8): 2398–407.
13. Mercuri E, Barisic N, Boespfug-Tangruy O, Day JW, et al. SUNFISH Part 2: Efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). Presented at: European Academy of Neurology (EAN) 2020- 6th Congress. May 23rd – May 26th, 2020; Paris, France.
14. Veerapandiyan A et al. Muscle Nerve 2020; 61(2): 222–6.
15. Jochman E et al. Ther Adv Neurol Disord 2020; 13: 1–11.
16. Hagenacker et al., Lancet Neurol 2020; 19: 317–25.
17. De Vivo DC et al. Neuromuscul Dis 2019; 29(11): 842–56.
18. WHO Multicentre Growth Reference Study Group. Acta Paediatr Suppl 2006; 450: 86–95.
19. Finkel RS et al. NEJM 2017; 377: 1723–32.
20. Strauss KA, Swoboda KJ, Farrar M, et al. AVXS-101 gene-replacement therapy in presymptomatic spinal muscular atrophy: SPR1NT study update. Communication presented at American Academy of Neurology 2019-71st Annual Meeting; May 4-10, 2019; Philadelphia, PA, USA.