Spinal muscular atrophy (SMA) is a serious neurodegenerative disease that is transmitted from parents to children (it is estimated that one in every 40-50 people is a healthy carrier of this pathology, one in every 10,000 babies suffers) and is due to the absence or dysfunction of the gene that produces the SMN protein. This genetic defect causes the loss of motor neurons in the spinal cord – which are responsible for movement – and, as a result, the muscles progressively weaken and stop working.
Affected babies are born apparently healthy and the disease can go unnoticed until the little ones begin to show symptoms when they are a few months old. Its early diagnosis is key to establishing treatment as soon as possible and avoiding the loss of motor neurons that causes disability, and even death in these children. Now, a new study has shown that newborn screening for spinal muscular atrophy and early treatment significantly improves its prognosis and allows little patients to be able to walk within two years of diagnosis.
Until recently there were few therapeutic options for SMA, but three treatments are now available – the drugs nusinersen and risdiplam, and the gene therapy onasemnogene abeparvovec (Zolgensma®) – approved by drug regulatory agencies in the United States and the European Union. However, these drugs are more effective if given early, especially before symptoms appear.
Children diagnosed with spinal muscular atrophy by neonatal screening walked better and had greater ability to move than children diagnosed by symptoms
The new study was conducted by researchers at the University of New South Wales in Sydney, Australia, and its results – which have been published in The Lancet Child & Adolescent Health – provide evidence for the first time that diagnosing children with SMA in the preclinical phase (before they manifest symptoms) through neonatal screening and early treatment modifies the natural progression of the disease in an important way.
Children with SMA who received early treatment were able to walk
The researchers compared data for children diagnosed with SMA after newborn screening was established in Australia (between 2018 and 2020) with those for diagnoses made before the start of that program (between 2016 and 2018). The screening pilot program began in New South Wales and the Australian Capital Territory and tracks the genes responsible for the disease with parental consent in a drop of blood from babies (the heel prick). a few days after birth.
Of the children diagnosed with neonatal screening, nine did not show symptoms of spinal muscular atrophy during the first weeks of life, so they were considered presymptomatic when receiving treatment. Two years after diagnosis, the infants’ ability to sit, crawl, stand, and walk, as well as other assessments of movement ability, were assessed.
Of the 14 children with SMA diagnosed by newborn screening who received early treatment, 11 were walking independently or with assistance two years after diagnosis, whereas only one of 16 children maintained that motor function when diagnosed based on their symptoms, which appear on average at four months of age. It was found that, in general, those who had been diagnosed by neonatal screening walked better and their capacity for movement and independence were greater than those of children diagnosed by symptoms, despite the fact that all those diagnosed by screening were smaller.
Neonatal screening, key in cases of spinal muscular atrophy
“Neonatal screening has been proposed as the gateway to early diagnosis of SMA and treatment at a more convenient time. However, until now evidence was lacking on the impact of such screening beyond clinical trial populations. Our study is the first to look at real-world data on how children with SMA diagnosed through newborn screening fare compared to children diagnosed after the development of symptoms. We believe that our findings justify a broader implementation of neonatal SMA screening”, says neuropediatrician Arlene D’Silva, from the University of New South Wales and one of the authors of the research.
For his part, Juan Francisco Vázquez, Coordinator of the Motor Neuron Diseases Unit in the Neuromuscular Diseases and Ataxias Unit of Hospital La Fe, contracted Juan Rodés, member of CIBERER and associate professor at the University of Valencia, has declared to SMC Spain that “the study confirms the data from clinical trials, which demonstrated much greater efficacy of treatment when patients are treated before the onset of symptoms. They also confirm the ‘real life’ results of other recent neonatal screening programs in other countries, which have shown great efficacy of treatments when they are started before the onset of symptoms”.
And he adds that “in any serious country neonatal screening should have already been implemented. Unfortunately, this is not the case in many countries (including Spain). This study provides further evidence on the importance of its implementation”. “In Spain, a national neonatal screening has not been implemented. Some CCAAs have pilot programs, the level of development and implementation is variable and I do not know why they have not been made public. Currently, the vast majority of newborns in Spain do not have access to neonatal screening.
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