Background: Disease modifying treatments (DMT) and implementation of newborn screening (NBS) have transformed management for those with SMA. Early DMT is associated with more favorable outcomes presumably due to stabilization and rescue of motor neurons. Clinical trials have demonstrated significant improvement in motor function (MF) for those treated presymptomatically.
Objectives: To assess real-world effectiveness of DMTs for SMA in those treated prior to 3-months of life.
Results: Twenty-one infants with SMA initiated DMT at an urban US site before 3-months of age. All had two follow-up visits; the majority had ≥ three. Ages at date of review ranged from 10.5 months to 8.42 years. Those diagnosed via NBS/prenatal screening (n=16) had a mean age of 31.3 months while the group diagnosed clinically, prior to implementation of NBS (n=5), had a mean age of 75.4 mo. Mean time to first DMT was 11.3 days (prenatally diagnosed group), 24.8 days (NBS diagnosed group) and 49.4 days (clinically diagnosed group). Time to first treatment did not vary by copy number but was significantly different (p=.05) between the NBS, prenatal and clinically identified groups. Nine infants were treated with monotherapy, the remaining 12 infants received more than one DMT, sequentially or in combination. All infants demonstrated gross motor improvements on MF measures, including SMA-specific and non SMA-specific norm-referenced assessments. Detailed MF results over time, as well as average age for acquisition of developmental skills and correlations with copy number and time to first DMT were explored.
Conclusions: Early identification and treatment facilitate optimal MF outcomes. This cohort adds to the evidence that NBS for SMA is associated with significantly earlier time to first treatment and is subsequently associated with improved MF including the ability to independently sit and ambulate within typical age ranges. This cohort also supports the inclusion of norm-referenced MF outcomes to expand breadth of assessment as most infants ceiling on the CHOP-INTEND before 1 year.
Prenatal diagnosis and/or short time intervals between a positive NBS result and subsequent referral to an urban therapy-ready specialized treatment center likely facilitated positive outcomes. Longer-term studies with larger numbers should be considered to further explore MF outcomes as well as systemic barriers creating unnecessary delays in treatment in this population.