Newborn screening for spinal muscular atrophy - what have we learned?

ABSTRACT

Introduction

Over the last decade, the treatment of spinal muscular atrophy (SMA) has become a paradigm of the importance of early and accurate diagnosis and prompt treatment. Three different therapeutic approaches that aims to increase SMN protein are approved now by Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of SMA; their efficacies have been demonstrated in pivotal trials.

Areas covered

The authors report on the two controlled studies and real-world evidence that have demonstrated that the treatment of patients pre-symptomatically ensures normal or only slightly sub-normal motor development in children who would otherwise develop a severe form of the disease. Furthermore, the authors highlight the several newborn screening (NBS) methods that are now available, all of which are based on real-time PCR, that reliably and robustly diagnose SMA except in subjects with disease caused by a point mutation.

Expert opinion

Pre-symptomatic treatment of SMA has been clearly demonstrated to prevent the most severe forms of the disease. NBS constitutes more than a simple test and should be considered as a global process to accelerate treatment access and provide global management of patients and parents. Even though the cost of NBS is low and health economics studies have clearly demonstrated its value, the fear of identifying more patients than the system can treat is often reported in large middle-income countries.

KEYWORDS:

• Spinal muscular atrophy
• SMN1
• SMN2
• Therapeutics
• newborn screening

Article highlights

• Three disease-modifying treatments have formally demonstrated their efficacy in the management of Spinal Muscular Atrophy

• There is compelling evidence from clinical trials and real world that treatment efficacy is highly dependent upon their timing of administration- the earlier the better

• Newborn screening has been implemented in several countries and has demonstrated high reliability to identify patients early, initiate treatments early and obtain the best treatment efficacy.

• The cost of treatments creates a significant inequity to access around the world. Newborn screening has been demonstrated to be highly cost-effective.

• Long-term data collection is needed to identify the best and most cost-effective treatments for patients identified by newborn screening.

Declaration of interest

L Servais has served as a consultant or as an advisory board member for Novartis, Biogen Idec, Roche, Scholar Rock, BioHaven, and Zentech. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.