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Published on: January 11, 2014
Longitudinal natural history of type I spinal muscular atrophy: a critical review
Eugenio Mercuri1,2, Simona Lucibello3,4, Marco Perulli3,4
1Paediatric Neurology, Catholic University, Rome, Italy. eugeniomaria.mercuri@unicatt.it.
Insights
Natural history studies in spinal muscular atrophy (SMA) are limited. This review of longitudinal data in infants with type I SMA found no improvement in CHOP INTEND scores over time, even in a larger cohort.
Area of Science:
- Neurology
- Pediatrics
- Genetics
Background:
- Limited natural history data exists for infants with type I spinal muscular atrophy (SMA).
- Structured assessments are crucial for understanding disease progression in SMA.
- New SMA therapies necessitate robust natural history data for comparison.
Purpose of the Study:
- To review existing longitudinal natural history data in infants with type I SMA.
- To analyze data from infants assessed before 7 months using the CHOP INTEND scale.
- To establish a baseline for comparing outcomes in treated SMA patients.
Main Methods:
- Identified and reviewed three longitudinal natural history studies (US and Italy).
- Included infants with type I SMA assessed before 7 months of age.
- Utilized the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for assessment.
Main Results:
- Cumulative analysis of a larger cohort confirmed no improvement in CHOP INTEND scores over time.
- This lack of improvement was consistent across all infants, regardless of age or baseline scores.
- Infants with neonatal onset SMA showed low scores and rapid decline; progression rates were calculated for subgroups based on SMN2 copy number and baseline scores.
Conclusions:
- Understanding natural history is vital due to the availability of disease-modifying therapies for SMA.
- This review provides insights into the variability of natural history in untreated SMA patients.
- Findings will aid in comparing real-world outcomes of treated patients with historical data.
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.
