Welcome to the WCN 2023 Interactive Program

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Spinal muscular atrophy (SMA) is degenerative disorder of the peripheral motoneuron due to a homozygous deletion of SMN1 gene coding for survival motoneuron protein. According to the age of onset, achieved motor abilities and life span; SMA is classified into 4 subtypes. Type 1 for congenital forms with hypotonia, feeding and respiratory deficiency; this is the most severe one responsible of death in most of cases. Type 2 for SMA where the first symptoms appear between the age of 6 and 18 months; the patient achieve rarely sitting and walking ability, with a risk of respiratory deficiency. In type 3 the first symptoms appear between the age of 3 and 18 years, with a variable functional disability and frequently normal life span. Type 4 is the least severe, beginning at adult age.The same mutation leads to different SMA phenotypes. This arises the question of existing phenotypic modifiers of the disease. SMN2 gene encodes the same protein as SMN1, but a silent transition within exon 7 results in a non-functional variant of SMN protein. Each SMN2 copy can produce only around 10% of functional SMN protein. Numerous studies show that the number of SMN2 copies is correlated to a milder disease phenotype in most of SMA cases. Thus, SMN2 copy numbers is considered as the most important phenotype modifier for the disease and was the basis of therapeutic targets in some of the recently developed treatments. However other genetic and biological markers of disease progression could be involved and remain an urgent matter in SMA research.

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Current clinical developments in Spinal Muscular Atrophy (SMA) converge to demonstrate the importance of early treatment, with even greater efficacy when treatment is pre-symptomatic. The identification of pre-symptomatic patients requires large-scale neonatal screening, which we have implemented in a pilot project in the Wallonia-Brussels Federation from March 2018. Initially covering the annual 17,000 births from the Liege Center, the program gradually expended to 3 screening centres and currently covers 120,000 births per year, i.e., all Belgium.

The cost and quality of life studies revealed a considerable impact of SMA on the daily life of patients and their families, but also on society, which bears the costs of health care. We conducted a medico-economic analysis to compare newborn screening for SMA followed by disease-modifying therapy with the comparator: usual care for patients diagnosed post-symptomatically. Newborn screening is associated with a substantial gain in quality of life (QALY), at a favorable cost per QALY gained, leading to the dominance of the strategy.

Given the motor evolution of patients treated before the onset of symptoms and the dramatic improvement in their health-related quality of life, newborn screening offers the possibility of improving the quality of life and life expectancy of SMA patients at a reasonable additional cost compared to no screening when treatments are available.

Abstract Body

Spinal Muscular Atrophy is a devastating condition. In the most severe and frequent form- SMA type 1- it leads to death or permanent ventilation within 2 years in newborns.

Three drugs have been recently approved : Intrathecal delivered nusinersen- orally delivered risdiplam and one-shot IV gene therapy onasemnogene abeparvovec.

The clinical development and the implementation of these drugs came with specific challenges that were exacerbated by the severity of the disease- the sequential availability of these drugs and global inequity to drug access. In addition- it rapidly became clear that early treatment was associated with much better outcome- prompting newborn screening programs to be initiated at different pace in several countries. The aim of this lecture will be to review the specific challenges that the community has faced- and the potential solution that could be proposed in conditions that new treatments will transform in the coming years.