ADVERTISEMENT
For Some Infants With Spinal Muscular Atrophy, Earlier Intervention May Be Warranted
New research has called into question the “watchful waiting” strategy for infants born with spinal muscular atrophy (SMA) and multiple copies of the SMN2 gene, according to a study published in the Journal of Neuromuscular Diseases. Researchers urge clinicians to take a “proactive approach [such as] early initiation of treatment in this subgroup of SMA patients.”
“Early treatment after genetic newborn screening (NBS) for SMA significantly improves outcomes in infantile SMA,” said lead author Dr Katharina Vill, Department of Pediatric Neurology and Development Medicine and LMU Center for Children with Medical Complexity, Dr von Hauner Children’s Hospital, LMU Hospital, Ludwig-Maximilians-University, Munich, Germany, and co-authors in the study background. “However, there is no consensus in the SMA treatment community about early treatment initiation in patients with 4 copies of SMN2.”
Previous guidelines have suggested that more than 2 copies of the SMN2 gene might guard against the neurodegeneration caused by defects in the SMN1 gene until late childhood or even adulthood. Still, researchers found that a significant proportion of infants with 4 copies of the SMN2 gene developed the first symptoms of SMA between ages 1.5 and 4 years.
News: Gene Therapy Improves Survival for Infantile Spinal Muscular Atrophy
The study involved 18 children with SMA and 4 copies of the SMN2 gene, born between January 2018 and January 2021, with long-term follow up feasible for 15 children. All reached the expected developmental benchmarks, including independent sitting, aided walking, and regular swallowing and feeding activity.
In 2020, midway through the study, treatment guidelines for SMA were changed, resulting in the recommendation to all patient families involved in the study to implement pre-symptomatic treatment. The families of 8 of the patients decided to initiate treatment with Nusinersen or Risdiplam in their children (ranging from 3 months to 36 months in age), while the families of 7 of the patients declined treatment per the “wait and see” strategy.
None of the 8 patients receiving pre-symptomatic treatment have shown any symptoms of SMA to date. In contrast, 5 of the 7 children not receiving treatment demonstrated disease onset between 1.5 and 4 years of age.
“While the sample size is small, a very high number of children (5 out of 7) became symptomatic in the first 4 years of life, with at least 1 showing irreversible symptoms. The proportion was much higher than expected,” Dr. Vill told IOS Press. “Children with 4 copies of SMN2 have the most favorable genetic conditions for a good outcome under therapy. The ‘wait and see’ strategy might entail the risk of irreversible deficits for these patients. We recommend encouraging parents to start a treatment regimen early in childhood. If the parents decide to wait, follow up should be performed with extreme care.”
References
