Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are severe,
progressive, and life-limiting neuromuscular disorders that manifest during early
childhood. Both conditions are characterized by motor function decline, leading to severe
disability and premature mortality. The availability of disease-modifying therapies has
dramatically changed the clinical landscape, but their effectiveness is strongly
dependent on very early initiation, ideally before symptom onset.
Newborn screening (NBS) for SMA has now been implemented in several countries, enabling
the identification of affected infants at birth. This shift creates a new challenge: the
need to monitor presymptomatic or minimally symptomatic children over time with
sensitive, reliable, and age-appropriate tools. Conventional motor function scales were
designed for older children and are not sufficiently adapted for infants and toddlers. As
a result, there is a critical gap in longitudinal assessment during the first years of
life, a period when therapeutic interventions may have the greatest impact.
The Active NBS study was designed to address this unmet need. This is a monocentric,
fully remote, academic, observational study that leverages wearable digital technologies
to monitor motor development in very young children with SMA or DMD. The study is
conducted entirely at a distance, with no requirement for hospital visits, thereby
reducing the burden on families and improving accessibility.
Study Objectives:
The primary objective is to validate digital biomarkers of early motor development in
children diagnosed with SMA or DMD. Secondary objectives include the early detection of
motor deficits, quantification of developmental delays according to genetic subtype, and
modeling of motor trajectories during the first years of life. Exploratory objectives
focus on gait analysis, including stride velocity 95th centile (SV95C), and comparisons
of motor outcomes across genetic backgrounds and treatment exposure.
Study Design and Procedures:
Up to 100 children will be enrolled, including infants identified by NBS, family testing,
or incidental diagnosis. Enrollment and informed consent are performed remotely using
secure electronic platforms. Participants are followed prospectively for up to 30 months,
with assessments every 6 months through structured questionnaires and video consultations
with the study team.
Two wearable devices will be employed, depending on the child's age and motor status:
MAIJU® (Motor Assessment of Infants with a Jumpsuit): a sensorized garment designed
for non-ambulant infants, capturing spontaneous movement and generating a composite
biomarker (Babacloud Infant Motility Score, BIMS).
Syde®: a wearable ankle sensor validated in ambulant children, enabling precise gait
monitoring and calculation of SV95C, a regulatory-accepted endpoint in DMD.
Data collected include digital motor endpoints, routine clinical information, and quality
of life metrics (PedsQL). Families are instructed on the correct use of devices and can
install and remove them independently at home. No travel or in-person assessments are
required, making this approach particularly suitable for rare disease populations.
Scientific Rationale:
Traditional motor scales, while validated in older children, lack sensitivity to detect
subtle developmental changes in infancy and early childhood. Digital endpoints derived
from continuous movement monitoring have the potential to provide richer, objective data
on motor development. By validating these measures in a presymptomatic or early
symptomatic population, this study aims to establish novel tools for both clinical
practice and future interventional trials. Importantly, the study also addresses the
practical and ethical challenges of long-term follow-up in very young children by
implementing a fully remote design.
Expected Impact:
The Active NBS study is expected to generate the first large-scale, longitudinal dataset
on motor development in presymptomatic and early symptomatic children with SMA and DMD.
The validation of digital endpoints such as SV95C and BIMS will contribute to the
development of sensitive outcome measures for clinical trials and may support regulatory
acceptance in the future. Beyond its immediate scientific goals, the study demonstrates
the feasibility and acceptability of decentralized follow-up in rare pediatric
populations, setting the stage for broader applications of digital health technologies in
neuromuscular disorders.
