Spinal Muscular Atrophy – Pre-Symptomatic Intervention 

Spinal Muscular Atrophy – Pre-Symptomatic Intervention 

The recently published Standards of Care for spinal muscular atrophy (SMA) promote more proactive and earlier approaches to the management of patients with severe SMA.1 These recommendations are likely based on the promising results of recent clinical trials that suggest that more effective treatments for SMA may be on the horizon as well as data that suggest that treatment provided earlier is more effective and may result in better motor functioning and longer survival.2–5 

It is important that knowledge and expectations of not only healthcare providers but also patients and caregivers evolve to account for new realities in our understanding SMA and how best to treat it.6 If the options for SMA treatment change, then so too should considerations for those deciding whether to diagnose or treat those at risk for SMA. 

Technological advances offer new relevant opportunities. For instance, a couple who is at risk of conceiving a child with SMA can now use in vitro fertilization and select embryos that are identified as unaffected through pre-implantation genetic testing.7

The ability to diagnose at-risk infants with SMA pre-symptomatically has led to much debate over whether pre-symptomatic SMA patients should be treated before they display symptoms.6,8,9 However, new research suggests that earlier treatment is more effective even in pre-symptomatic patients,10 which may change the substance of this debate.

Regardless of what is determined appropriate in terms of pre-symptomatic intervention, guidelines and clinical decision making should incorporate and consider the latest data on pre-symptomatic intervention. Similarly, patients, caregivers, and loved ones should be provided with the most comprehensive and up-to-date picture of what pre-symptomatic intervention will mean in the context of their situation so that they can make the best, most informed choices for relevant therapy. In this constantly evolving field, there is likely not to be a one-size-fits-all intervention, and what appears to be the best option for any given patient may change over time. 

References

1. Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute  care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197-207. doi:10.1016/j.nmd.2017.11.004

2. Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1723-1732. doi:10.1056/NEJMoa1702752

3. Mendell, JR, Al-Zaidy, S, Shell R. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377:1713-1722.

4. Foust, KD, Wang, X, McGovern V. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010;28:271-274.

5. Hua Y, Sahashi K, Rigo F, et al. Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature. 2011;478(7367):123-126. doi:10.1038/nature10485

6. Tizzano EF, Zafeiriou D. Prenatal aspects in spinal muscular atrophy: From early detection to early presymptomatic intervention. Eur J Paediatr Neurol. 2018;22(6):944-950. doi:10.1016/j.ejpn.2018.08.009

7. Girardet A, Fernandez C, Claustres M. Efficient strategies for preimplantation genetic diagnosis of spinal muscular atrophy. Fertil Steril. 2008;90(2):443.e7-12. doi:10.1016/j.fertnstert.2007.07.1305

8. Tizzano EF, Finkel RS. Spinal muscular atrophy: A changing phenotype beyond the clinical trials. Neuromuscul Disord. 2017;27(10):883-889. doi:10.1016/j.nmd.2017.05.011

9. Glascock J, Sampson J, Haidet-Phillips A, et al. Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening. J Neuromuscul Dis. 2018;5(2):145-158. doi:10.3233/JND-180304

10. Bertini E et al. Efficacy and safety of nusinersen in infants with presymptomatic spinal muscular atrophy (SMA): Interim results from the NURTURE study. Eur J Paediatr Neurol. 2017;21:e14.