SMA in Late February: Roche’s Sunfish Trial, Intrathecal Nusinersen Treatment & More

Nisha Cooch, PhD avatar

by Nisha Cooch, PhD |

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Perhaps the biggest SMA news this month has been the success of Roche’s Sunfish trial, but fundamental research, such as those into the mechanisms of the disease and the implications of certain interventions, continue. 

Below is a roundup of the latest news and literature on SMA.

Understanding SMA

Survival motor neuron protein participates in mouse germ cell development and spermatogonium maintenance.1

This article builds on the authors’ previous work showing that SMN plays a role in stem cell biology and the development of germ cells. The researchers show that SMN is expressed at high levels in gonadal tissues, prepubertal spermatogonia, and adult spermatocytes in healthy mice, whereas in an SMA mouse model, the growth of tissues of the testes are retarded. These tissue abnormalities are also accompanied by changes in gamete development and spermatogonia-specific marker loss. The authors conclude that SMN is involved not only in neuronal development but also in the maintenance of mouse germ cell and spermatogonium. 

Read more here. 

The analysis of the association between the copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein genes and the clinical phenotypes in 40 patients with spinal muscular atrophy: Observational study.2

In this article, researchers describe their investigation into the relationship between SMN2 and neuronal apoptosis inhibitory protein (NAIP) copy number variance and SMA phenotype. They used multiplex ligation-dependent probe amplification assays to identify relevant copy numbers from 40 SMA patients. The scientists found that fewer copies of these genes increased the likelihood of earlier SMA onset and earlier death. Based on these findings, the authors conclude that SMN and NAIP copy number may provide value in predicting disease progression and informing genetic counseling.

Read more here. 

Recent Reviews:

  • The role of RNA binding proteins for local mRNA translation: Implications in neurological disorders.3

Disruption to neuronal protein homeostasis can lead to neurological disorders like SMA. This review provides a comprehensive summary of the role of relevant proteins, including well-known RNA binding proteins, in neuronal function. Additionally, the authors provide information on how these proteins may contribute to pathology including SMA.

Read the review here. 

Treating SMA

Drug treatment for spinal muscular atrophy types II and III.6

This article describes a study into the efficacy and safety of drug treatments to slow or halt SMA type 2 and SMA type 3 disease progression. Based on a comprehensive analysis, the authors determined that there is evidence to suggest that nusinersen improves motor function for those with SMA type 2 and that olesoxime and somatropin may have some clinically meaningful effects on SMA patients. The authors also suggest that there is no clinically relevant impact of creatine, gabapentin, hydroxyurea, phenylbutyrate, or valproic acid. In addition, the authors state that the evidence regarding nusinersen can be regarded as moderate-certainty evidence, whereas the other findings are based on low or very low-certainty evidence.

Read the review here. 

Intrathecal nusinersen administration in adult spinal muscular atrophy patients with complex spinal anatomy.7

This paper describes a study aimed at addressing the question of whether nusinersen treatment should be pursued in SMA patients with complex spinal anatomy. As spine deformity is common in SMA, so too are surgeries that can leave patients with implantations that make intrathecal administration difficult or impossible. Based on their analysis of 53 CT-guided lumbar punctures in patients with SMA type 2 and SMA type 3 who also suffered from scoliosis, the authors determined that nusinersen can be safely and successfully administered even in the case of complex spinal anatomy. They also point to the option of translaminar drilling in the case that intrathecal administration is not possible. They conclude that nusinersen treatment should not be withheld from this population of patients.

Read the review here. 

Circulating myomiRs as potential biomarkers to monitor response to nusinersen in pediatric SMA patients.4

Dysregulation of microRNAs contributes to neuromuscular diseases like SMA. In this paper, the authors describe their study of muscle-specific miRNAs (myomiRs) in 21 infants with SMA. The researchers examined serological levels of several of these myomiRs before nusinersen treatment and after 6 months of treatment and found that levels of myomiRs decreased with treatment. Additionally, they found that reduced miR-133a levels predicted treatment response. They therefore conclude that myomiRs may serve as valuable biomarkers for monitoring SMA progression and therapeutic response.

Read more here.

Recent Reviews:

  • Twenty-five years of spinal muscular atrophy research: From phenotype to genotype to therapy, and what comes next.5

This piece provides a comprehensive review of what is known about SMA phenotypes and genotypes and where we are in terms of SMA therapy. It describes some of the major milestones that have led to the therapies currently available for SMA patients and discusses the direction of treatment and SMA screening.

Read the review here. 

Managing SMA

Evaluation of body composition as a potential biomarker in Spinal Muscular Atrophy.8

In this study, researchers describe their investigation into a potential relationship between body composition and motor function in those with SMA. Based on their study of 88 children ranging in age from 1 to 10 years and who had been diagnosed with SMA type 1 or SMA type 2, the authors observed that motor function in this patients was associated with specific aspects of body composition including body mass index (BMI). They therefore conclude that body composition may serve as a biomarker for SMA.

Read more here. 

Impact of scoliosis surgery on pulmonary function in patients with muscular dystrophies and spinal muscular atrophy.9

Scoliosis is common in those with SMA, as are relevant surgical procedures. This study aimed to identify any potential impact of posterior spinal fusion on pulmonary function in those with neuromuscular diseases like SMA. The researchers found that spinal fusion was associated with a loss of vital capacity in those with SMA, whereas it was associated with an increase in vital capacity in those with merosin deficient muscular dystrophy. More research is needed to determine the details of how and why spinal fusion impacts pulmonary function.

Read more here. 

Patient Focus and Policy Implications

The prevalence of spinal muscular atrophy carrier in China: Evidences from epidemiological surveys.11

There has been recent interest in the prevalence of SMA carriers in China, for which there has previously been no detailed analysis. This piece represents a new analysis that has determined that the overall carrying rate of SMA in China is as high as 2% and growing. The authors suggest that more research is needed to understand this prevalence and the upward trend so that the disease can be better controlled. 

Read more here.

A prospective crossover survey study of child- and proxy- reported quality of life according to spinal muscular atrophy type and medical interventions.12

As our understanding of SMA increases and more medical interventions become available, life for those with disease is changing in quality and duration. Maintaining an understanding of how patients and caretakers feel about outcomes associated with specific interventions is critical as we continue to pursue SMA research and find ways translate research findings into meaningful clinical practice. This study aimed to identify the effects of specific interventions on children’s perceived quality of life and how these perceptions may differ from others’ perceptions. The researchers found that children often reported their quality of life as higher than did those around them and that spinal surgery was associated with improved quality of life for SMA patients’ family members.

Read more here.

An assessment of the knowledge, attitudes, and practices of patients and families with diagnoses of hereditary neuromuscular disroders.13

This paper describes a study into gaps in knowledge amongst SMA patients and patients with other neuromuscular disease and how misconceptions may inform attitudes toward their diagnoses. The researchers evaluated data from 130 patients whose average age was 26.3. They found that nearly 80% of these patients mistakenly believed that their disease was curable and that more than half believed that they should avoid physical activity. The researchers point to the need for more education for patients, families, and communities to ensure that knowledge is accurate, expectations are realistic, and that appropriate interventions are undertaken.

Read more here.


Roche releases full report from Sunfish trial.

Earlier this month, Roche released their data on the effects of their drug risdiplam on patients with SMA type 2 and SMA type 3. Data from this “Sunfish trial” showed that the drug can improve motor function, particularly in patients between the ages of 2 and 25. Read more here.


1. Chang W-F, Xu J, Lin T-Y, et al. Survival Motor Neuron Protein Participates in Mouse Germ Cell Development and Spermatogonium Maintenance. Int J Mol Sci. 2020;21(3). doi:10.3390/ijms21030794

2. Zhang Y, He J, Zhang Y, et al. The analysis of the association between the copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein genes and the clinical phenotypes in 40 patients with spinal muscular atrophy: Observational study. Medicine (Baltimore). 2020;99(3):e18809. doi:10.1097/MD.0000000000018809

3. Thelen MP, Kye MJ. The Role of RNA Binding Proteins for Local mRNA Translation: Implications in Neurological Disorders. Front Mol Biosci. 2019;6:161. doi:10.3389/fmolb.2019.00161

4. Bonanno S, Marcuzzo S, Malacarne C, et al. Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in  Pediatric SMA Patients. Biomedicines. 2020;8(2). doi:10.3390/biomedicines8020021

5. Wirth B, Karakaya M, Kye MJ, Mendoza-Ferreira N. Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next. Annu Rev Genomics Hum Genet. January 2020. doi:10.1146/annurev-genom-102319-103602

6. Wadman RI, van der Pol WL, Bosboom WM, et al. Drug treatment for spinal muscular atrophy types II and III. Cochrane database Syst Rev. 2020;1:CD006282. doi:10.1002/14651858.CD006282.pub5

7. Cordts I, Lingor P, Friedrich B, et al. Intrathecal nusinersen administration in adult spinal muscular atrophy patients with complex spinal anatomy. Ther Adv Neurol Disord. 2020;13:1756286419887616. doi:10.1177/1756286419887616

8. Baranello G, De Amicis R, Arnoldi MT, et al. Evaluation of body composition as a potential biomarker in Spinal Muscular Atrophy. Muscle Nerve. February 2020. doi:10.1002/mus.26823

9. Farber HJ, Phillips WA, Kocab KL, et al. Impact of scoliosis surgery on pulmonary function in patients with muscular dystrophies and spinal muscular atrophy. Pediatr Pulmonol. February 2020. doi:10.1002/ppul.24664

10. Gayduk AI, Vlasov Y V. [Spinal muscular atrophy in samara region. Epidemiology, classification, prospects for health care]. Zhurnal Nevrol i psikhiatrii Im SS Korsakova. 2019;119(12):88-93. doi:10.17116/jnevro201911912188

11. Li C, Geng Y, Zhu X, et al. The prevalence of spinal muscular atrophy carrier in China: Evidences from epidemiological surveys. Medicine (Baltimore). 2020;99(5):e18975. doi:10.1097/MD.0000000000018975

12. Weaver MS, Hanna R, Hetzel S, et al. A Prospective, Crossover Survey Study of Child- and Proxy-Reported Quality of Life According to Spinal Muscular Atrophy Type and Medical Interventions. J Child Neurol. February 2020:883073819900463. doi:10.1177/0883073819900463

13. Mohiuddin Ahmed H, Advani R, Arif AA, Khan S. An Assessment of the Knowledge, Attitudes, and Practices of Patients and Families with Diagnoses of Hereditary Neuromuscular Disorders. Neuroepidemiology. February 2020:1-7. doi:10.1159/000505330