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Spinal Muscular Atrophy – Key Information

This information sheet is written for anyone wanting to know more about Spinal Muscular Atrophy (SMA).

What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a rare, genetically inherited neuromuscular condition. It causes progressive muscular weakness and loss of movement due to muscle wasting (atrophy). This may affect crawling and walking ability, arm, hand, head and neck movement, breathing and swallowing.

There are four main types of SMA:

  • SMA Type 1: symptoms begin between the ages of 0 and 6 months. It is the most severe form of SMA. Babies are unable to sit without support. Sadly, without intervention most children with SMA Type 1 rarely survive beyond two years of age, usually due to breathing difficulties.
     
  • SMA Type 2: symptoms begin between the ages of 7 and 18 months. Children with SMA Type 2 are unable to stand without support. Though this is a serious neuromuscular condition that may shorten life expectancy1, improvements in care standards mean that the majority of people can live long, fulfilling lives.
     
  • SMA Type 3: symptoms begin after 18 months of age. Children can stand and walk, although this will become more difficult and they will need more support with this over time. Life expectancy for children diagnosed with SMA Type 3 is not affected2 and most people can live long, fulfilling lives.
     
  • SMA Type 4: symptoms begin in adulthood and include mild to moderate muscle weakness in the arms and legs and some difficulty walking. SMA Type 4 is not life-threatening3.

These ‘Types’ are not rigid categories. There is a wide spectrum of severity both between the different types of SMA and between individuals within each type.  There are also other even rarer forms of childhood and adult-onset SMA.

For more information about diagnosis and the different types and rarer forms of SMA, visit: www.smasupportuk.org.uk/about-sma

What causes the main types of SMA?

  • The SMN1 gene

The main types of SMA affect the nerve cells called lower motor neurons which reside in the spinal cord and project out to the muscles. These lower motor neurons carry electrical signals from the brain to move the muscles used for crawling and walking. These signals also control movement of arms, hands, head and neck as well as breathing and swallowing. For these lower motor neurons to be healthy, our Survival Motor Neuron 1 genes (SMN1 genes4) must produce enough Survival Motor Neuron (SMN) protein.

Most people have two copies of the SMN1 gene. People with the main types of SMA have two faulty copies of the SMN1 gene, which means they are unable to produce enough SMN protein to have healthy lower motor neurons3. This causes their lower motor neurons in the spinal cord to deteriorate. This restricts the delivery of signals from the brain to their muscles, making movement difficult. Their muscles then waste due to lack of use; this is known as muscular atrophy.

In summary:

The SMN1 gene is on the fifth chromosome in the region labelled ‘q’. This is why the main types of SMA are often referred to as ‘5q SMA’.

  • The SMN2 gene4

A second gene also has a role in producing SMN protein. This is the Survival Motor Neuron 2 gene (SMN2), sometimes referred to as the SMA “back-up gene”. 

However, most of the SMN protein produced by SMN2 lacks a key building block that is usually produced by SMN1. This means that SMN2 cannot fully make up for the faulty SMN1 gene in people with SMA. 

The number of SMN2 genes can vary greatly from person to person, from 0 – 8 copies. The severity of SMA has been linked to how much SMN protein a person makes5-7; individuals with more SMN2 copies typically have a less severe form of SMA than those with fewer copies.

How do people get SMA?

SMA is an autosomal, recessive, inherited neuromuscular condition. It is passed from parents to their children through faulty SMN1 genes:

  • People who have inherited two faulty copies of the SMN1 gene (one from each parent) have SMA.
     
  • People who have inherited one faulty copy and one healthy copy of the SMN1 gene (one from each parent) are carriers of SMA. Carriers usually do not have SMA or any symptoms of SMA.
     
  • People who have inherited two healthy copies of the SMN1 gene (one from each parent) do not have SMA and are not carriers.

When two SMA carriers have a child together, for each pregnancy there is a:

  • 1 in 4 (25%) chance that the child will inherit both faulty copies of the SMN1 gene and will develop SMA.
     
  • 1 in 2 (50%) chance that the child will inherit one faulty copy and one healthy copy of the SMN1 gene and will be a carrier.
     
  • 1 in 4 (25%) chance that the child will inherit two healthy copies of the SMN1 gene and will not be a carrier or have SMA.

In around 2% of cases of SMA, the mutation is new in the affected person, most likely due to an error in making the egg or sperm cell from which they were conceived.  This is called a de novo mutation

For more detailed information, please see our information sheet: The Genetics of SMA.         

How many people are affected?

Approximately 1 in 40 people carry the faulty SMN1 gene8 -  that means there are around 1.6 million carriers in the UK.

The incidence is the number of new cases of a condition or disease at any one time. Recent studies indicate that approximately one in every 10,000 babies worldwide are born with a type of SMA and that Type 1 SMA accounts for approximately 60% of cases8,9.

In the UK in 2016, there were 774,835 live births10-12. This suggests that in that year approximately 78 babies were born with a type of SMA.

The prevalence is how many people are living with a condition or disease in a population at any one time. Recent studies suggest between 1 and 2 people in every 100,000 worldwide have a type of SMA8,9.

In 2016, the UK population was 65.6 million13. Based on this, it is estimated that between 650 and 1300 people have SMA in the UK at any one time. Previous estimates by clinicians have suggested an upper limit likely to be 2,500. As there is no central information source, the exact numbers are unknown.

Is there a treatment or cure?

Although there is currently no cure for SMA, this does not mean that nothing can be done. There are a range of options aimed at managing symptoms, reducing complications of muscle weakness and maintaining the best quality of life. These are outlined in the internationally agreed Standards of Care for SMA14,15. These are currently being updated16.

There is a considerable amount of research into SMA taking place around the world. This research will not only improve our understanding of the condition, but will also help to develop effective treatments.

One area of extensive research is the genetics of SMA and the underlying mechanisms that lead to damage of the nerve cells. The UK is a significant contributor to this, with several UK centres involved in clinical trials and international collaborations. This has led to encouraging breakthroughs in developing treatments.

  • Nusinersen / SpinrazaTM

The first (and currently, the only) potentially available treatment for SMA is called nusinersen. Essentially, the drug is designed to modify the product of the SMN2 gene to produce more functional SMN protein. In collaboration with researchers, nusinersen was developed by Ionis Pharmaceuticals and Biogen Idec, which have run clinical trials with infants and children affected by SMA Types 1, 2 or 3. There have not yet been any clinical trials of nusinersen with anyone with SMA Type 4. To find out more about how nusinersen works and what the clinical trial results have been, please explore the nusinersen section of our website here.    

In September 2016, the positive results of the clinical trials for children with SMA Type 1 led Biogen to want to make it available as quickly as possible to others. They therefore launched a global Expanded Access Programme (EAP) for eligible infants with SMA Type 1. This was before they made any application for a licence to market the drug. Through the scheme, Biogen funds the drug for free while the costs of administration are met by the country where treatment is delivered.

On June 1st 2017,the European Commission approved nusinersen for marketing under its brand name SpinrazaTM as a treatment for those with 5q SMA17. This is a broad term, that includes SMA Types 1, 2, 3 and 4. However, nusinersen’s availability in the UK (other than via the EAP for those eligible with SMA Type 1) depends upon the outcome of reviews by regulatory authorities, of the evidence gained from clinical trials in each subtype of SMA and the costs of provision. They also consider submissions from the patient community and clinicians. The regulatory authorities include the National Institute for Health and Care Excellence (NICE), NHS England, the Scottish Medicines Consortium and other authorities in the devolved nations.

On 7th May 2018, the Scottish Medicines Consortium completed its review of whether it would recommend funding of nusinersen treatment for those with SMA Types 1, 2 and 3. They announced that they advised nusinersen treatment should be funded by the Scottish NHS for those with SMA Type 1 only. You can read more about this and any further updates about access in Scotland here           

NICE is currently considering whether to recommend funding in England for those with SMA Types 1,2 ,3 and 4.  They will announce their recommendation on November 21st 2018. You can read any updates about how this review is progressing here 

  • Other research developments

SMA Support UK’s website also notifies the SMA community about the latest developments with other drug treatments, the science behind them, and what clinical trials and other research is going on here . We alert people to new postings via our social media and monthly E-news. You can sign up for mailings here.           

References

  1. Farrar MA, Vucic S, Johnston HM, duSart D, Kiernan MC (2013) Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy. J Pediatrics 162: 155-159.
     
  2. Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I (1997) A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci 146: 67-72.
     
  3. Lunn MR, Wang CH (2008) ‘Spinal muscular atrophy’, Lancet, 371: 2120-2133.
     
  4. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J (1995) Identification and characterization of a spinal muscular atrophy-determining geneCell 80: 155-165.
     
  5. Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J (1997). Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16: 265–269.
     
  6. Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AHM, Prior TW (2002). Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med 4: 20–26.
     
  7. UK North Star and SMA-REACH clinical networks and SMA Support UK, TreatSMA and SMA Trust (2017) Letter to Edmund Jessop, 23 August. Available at: http://www.smasupportuk.org.uk/files/files/Research/August%2017/
    Nusinersen%20letter%20August%202017.pdf

    (Accessed: 11 March 2018)
     
  8. Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, Cook SF, Lochmüller H (2017) Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy –a literature review. Orphanet J Rare Dis 12: 124.
     
  9. Verhaart IEC, Robertson A, Leary R, McMacken G, König K, Kirschner J, Jones CC, Cook SF, Lochmüller H. (2017) A multi-source approach to determine SMA incidence and research ready population. J Neruol 264: 1465-1473.
     
  10. Office of National Statistics (2017) ‘Births in England and Wales: 2016’. Available at:
    https://www.ons.gov.uk/peoplepopulationandcommunity/births
    deathsandmarriages/livebirths/bulletins/birthsummarytablesenglandand
    wales/2016
    (Accessed:11 March 2018)
     
  11. National Records of Scotland (2017) ‘Births, Death and other Vital Events: Preliminary figures for 2016’. Available at: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/births-deaths-and-other-vital-events-preliminary-annual-figures/2016 (Accessed: 11 March  2018)
     
  12. Northern Ireland Statistics and Research Agency (2017) 'Monthyl births’. Available at: www.nisra.gov.uk/publications/monthly-births(Accessed:11 March 2018)
     
  13. Office for National Statistics ‘Overview of the UK Population: July 2017.’ Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/
    populationandmigration/populationestimates/articles/overview
    oftheukpopulation/july2017#main-points
    (accessed 11 March 2018)
     
  14. TREAT-NMD (2007) ‘Standards of care for Spinal Muscular Atrophy: Guide for families and family doctors’. Available at: http://www.treat-nmd.eu/care/sma/family-guide/
    (Accessed 11 March 2018)
     
  15. Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A, Wong B, Aloysius A, Morrison L, Main M, Crawford TO, Trela A; Participants of the International Conference on SMA Standard of Care (2007) Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 22: 1027-1049. Available at: www.treat-nmd.eu/care/sma/care-standards/
    (Accessed: 11 March 2018)
     
  16. Finkel RS, Sejersen T, Mercuri E; ENMC SMA Workshop Study Group (2017) 218th ENMC International Workshop: Revisiting the consensus on standards of care in SMA Naarden, The Netherlands, 19-21 February 2016. Neuromuscul Disord 27: 596-605.
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  17. European Medicines Agency (2017) ‘Committee for Medicinal Products for Human Use Assessment Report Spinraza’ (EMA/289068/2017). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004312/WC500229706.pdf
    (Accessed: 11 March 2018)
     

Version 3.4
Author: SMA Support UK Information Production Team
First published: September 2017

Updated: May 2018
Next full review due: September 2020

 

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