The recent decision of the federal Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) to recommend SMA for addition to the RUSP, as well as the implementation of SMA newborn screening (NBS) by several states, has ushered in the ability to identify infants with SMA before the onset of disease symptoms. To aid clinicians and the families they serve in the decision of when to administer therapy to infants identified with SMA via NBS, a working group led by Cure SMA and comprised of 15 SMA experts has developed treatment guidelines. These guidelines were recently published in the Journal of Neuromuscular Diseases in an article titled, “Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening”.
Thus far, both clinical and preclinical data indicate that early treatment will be critical to modulate the rapid and progressive degeneration seen in SMA, especially in type 1. The identification of SMN1 deletion combined with determination of SMN2 copy number is a powerful predictor of disease type and severity. Because of this strong correlation, the treatment algorithm is based upon SMN2 copy number. The overarching recommendation from the working group is that all infants with two or three copies of SMN2 should receive immediate treatment with an SMN-upregulating therapy. For those infants with 4 or more copies of SMN2, consensus was not reached. 50% of the working group was in favor of immediate treatment and 50% in favor of watchful waiting. Therefore, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation in infants for whom treatment is not immediately initiated.
The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help inform the treatment and follow-up of infants who test positive during the newborn screening process.
We thank our partners in the SMA Newborn Screening Coalition—Biogen, AveXis, and Genentech/Roche—for their support of this important issue.