Review

. 2020 Apr 5;15(1):84.

doi: 10.1186/s13023-020-01356-1.

Longitudinal natural history of type I spinal muscular atrophy: a critical review

Eugenio Mercuri^{1

2}, Simona Lucibello^{3

4}, Marco Perulli^{3

4}, Giorgia Coratti^{3

4}, Roberto de Sanctis⁴, Maria Carmela Pera^{3

4}, Marika Pane⁴, Jacqueline Montes^{5

6}, Darryl C de Vivo⁶, Basil T Darras⁷, Stephen J Kolb^{8

9}, Richard S Finkel¹⁰

Affiliations

¹ Paediatric Neurology, Catholic University, Rome, Italy. eugeniomaria.mercuri@unicatt.it.
² Centro Clinico Nemo, Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. eugeniomaria.mercuri@unicatt.it.
³ Paediatric Neurology, Catholic University, Rome, Italy.
⁴ Centro Clinico Nemo, Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁵ Departments of Rehabilitation and Regenerative Medicine, Columbia University Medical Center, New York, USA.
⁶ Department of Neurology, Columbia University Medical Center, New York, USA.
⁷ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁹ Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁰ Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, USA.

PMID: 32248834
PMCID: PMC7132885
DOI: 10.1186/s13023-020-01356-1

Review

Longitudinal natural history of type I spinal muscular atrophy: a critical review

Eugenio Mercuri et al. Orphanet J Rare Dis. 2020.

. 2020 Apr 5;15(1):84.

doi: 10.1186/s13023-020-01356-1.

Authors

Affiliations

¹ Paediatric Neurology, Catholic University, Rome, Italy. eugeniomaria.mercuri@unicatt.it.
² Centro Clinico Nemo, Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. eugeniomaria.mercuri@unicatt.it.
³ Paediatric Neurology, Catholic University, Rome, Italy.
⁴ Centro Clinico Nemo, Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁵ Departments of Rehabilitation and Regenerative Medicine, Columbia University Medical Center, New York, USA.
⁶ Department of Neurology, Columbia University Medical Center, New York, USA.
⁷ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁹ Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁰ Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, USA.

PMID: 32248834
PMCID: PMC7132885
DOI: 10.1186/s13023-020-01356-1

Abstract

Background: The advent of new therapies in spinal muscular atrophy (SMA) has highlighted the need to have natural history data for comparison. Natural history studies using structured assessments in type I however are very limited. We identified and reviewed all the existing longitudinal history data in infants with type I SMA first assessed before the age of 7 months with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).

Main text: Three longitudinal natural history studies, two performed in the United States and one in Italy, were identified. The different study design of these three studies made it possible for the cumulative dataset to include the full spectrum of severity; from infants with neonatal onset to those with a milder phenotype that were not always included in the individual natural history studies. The cumulative analysis confirmed that, even in a larger cohort, there was never an improvement on the CHOP INTEND over time. This was true for all the infants, irrespective of their age or baseline CHOP INTEND scores. Infants with neonatal onset had low CHOP INTEND scores and a fast decline. The relatively large number of patients allowed us to calculate the rate of progression in subgroups identified according to SMN2 copy number and baseline CHOP INTEND scores.

Conclusion: A detailed understanding of the existing data is important, as it will be difficult to acquire new systematic longitudinal history data because of the availability of disease modifying therapies. The cumulative findings in this review help to better understand the variability of natural history data in untreated patients and will be of use for comparison to the real world patients treated with the recently approved therapies that have shown encouraging results in clinical trials.

Keywords: CHOP INTEND; Natural history; Spinal muscular atrophy.

PubMed Disclaimer

Conflict of interest statement

Eugenio Mercuri has received funding as a member of advisory boards for SMA studies for AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, Scholar Rock and Roche; principal investigator for ongoing Ionis Pharmaceuticals, Inc./Biogen, Avexis and Roche clinical trials; funding from Famiglie SMA Italy, Italian Telethon, Biogen and SMA Europe.

Dr. Giorgia Coratti received funding from Biogen, Roche, Avexis and Genesis Pharma as speaker in sponsored symposia.

Dr. Roberto de Sanctis received funding from Biogen and Avexis as speaker in sponsored symposia.

Dr. Maria Carmela Pera received funding from Roche as speaker in sponsored symposia.

Dr. Marika Pane received funding as a member of advisory boards from Biogen and Avexis and as speaker in sponsored symposia.

Dr. Jacqueline Montes receives support from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) 1K01HD084690-01A1 and reports serving as a consultant for Ionis pharmaceuticals and Biogen, and serves on advisory boards for Roche Pharmaceuticals and Biogen.

Dr. Darryl C. de Vivo has received personal compensation for activities with AveXis, Biogen, Roche, IONIS, Sarepta, Cytokinetics Pharmaceuticals, and the SMA Foundation and has received research support from NIH, DOD, SMA Foundation, and Hope for Children Research Foundation.

Dr. Basil T. Darras has been a scientific advisory board consultant for AveXis, Biogen, Cytokinetics, Marathon, PTC, Roche, and Sarepta; advisor for Ionis Pharmaceuticals, Inc.; research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, and the SMA Foundation; grants from Ionis Pharmaceuticals, Inc., Biogen, Cytokinetics, Fibrogen, PTC, Sarepta, and Summit.

Dr. Stephen J. Kolb has been a scientific advisory board consultant for AveXis, Genentech and Biogen.

Dr. Richard S. Finkel Richard Finkel has received personal compensation for activities with Ionis Pharmaceuticals, Biogen, AveXis, Capricor, Catabasis, Lilly, Roche, Novartis; and the SMA Foundation, SMA Europe and Cure SMA as a consultant or advisor. Dr. Finkel has received research support from Ionis Pharmaceuticals, Biogen, Lilly, Cytokinetics Sarepta, NIH, MDA, and Summit.

Dr. Simona Lucibello, Dr. Marco Perulli have nothing to disclose.

Figures

**Fig. 1**
Individual CHOP-INTEND details of the 38 infants included: Figure shows the individual details of the 38 infants included: in green NeuroNEXT (Kolb et al., 2018); in red PNCR (Finkel et al., 2014), in blue Italian group (De Sanctis et al., 2018). Dotted line represent 3 SMN2 copies, black line 4 SMN2 copies

**Fig. 2**
Details of NH patients selected by ENDEAR criteria: Figure shows CHOP-INTEND scores by age of NH patients with 2 SMN2 copies with onset after the neonatal period. [•] represent patient with CHOP-INTEND baseline scores above 25; [•] represent those with baseline score between 25 and 35; [•] represent those with baseline score below 35. The interpolation line represents the CHOP-INTEND progression subdivided by baseline score (—) if above 35; (—) if between 25 and 35; (--) if below 25

See this image and copyright information in PMC

References

1. Bach JR. Medical considerations of long-term survival of Werdnig-Hoffmann disease. Am J Phys Med Rehabil. 2007;86:349–355. doi: 10.1097/PHM.0b013e31804b1d66. - DOI - PubMed
1. Borkowska J, Rudnik-Schoneborn S, Hausmanowa-Petrusewicz I, Zerres K. Early infantile form of spinal muscular atrophy (Werdnig-Hoffmann disease) with prolonged survival. Folia Neuropathol. 2002;40:19–26. - PubMed
1. Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics. 2004;114:e548–e553. doi: 10.1542/peds.2004-0668. - DOI - PubMed
1. Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83:810–817. doi: 10.1212/WNL.0000000000000741. - DOI - PMC - PubMed
1. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22:1027–1049. doi: 10.1177/0883073807305788. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Longitudinal natural history of type I spinal muscular atrophy: a critical review

Affiliations

Longitudinal natural history of type I spinal muscular atrophy: a critical review

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms