SMA in Focus: Practical Insights from MDA 2026

Twelve-Week Extension to STEER Study Finds Sustained Motor Function Gains With Intrathecal Onasemnogene Abeparvovec

A late-breaking abstract at the Muscular Dystrophy Association annual meeting provided an update from the phase 3 STEER trial, which evaluated the intrathecally administered formulation of  onasemnogene abeparvovec for treatment-naïve patients with spinal muscular atrophy (SMA) ages 2  to 17  years who could sit but not walk independently. The results of STEER’s main 52-week trial are reported in our coverage of Dr. Shieh’s presentation.

In the main study protocol, 126 patients with SMA were randomized to receive either the study medication (N = 75) or sham (N = 51) and followed for 52 weeks. Their motor function was assessed by the Hammersmith Functional Motor Scale-Expanded (HFMSE) score and Revised Upper Limb Module (RULM) score. In the extension study, those who completed the 52-week phase were entered into an additional 12-week phase, in which patients who originally received the control intervention were switched to an active intrathecal medication, and those who received active therapy during the initial phase were switched to a sham injection. For those who originally received onasemnogene abeparvovec (67 of the 75 patients continued to the second phase), mean HFMSE scores continued to increase, from a least-squares mean improvement from baseline of 2.39 points at week 52 and 2.75 points by week 64. For the RULM score, the mean increase from baseline was 2.44 points, and 2.93 at week 64.

Adverse events for the extension study were not significantly different compared with the first 52 weeks of STEER. Transaminase concentrations were mildly elevated and were transient.

The researchers concluded that motor function improvement continued in patients with SMA 64 weeks after intrathecal administration of onasemnogene abeparvovec.

Impact of Newborn Screening and Early Disease-Modifying Treatment on Motor Function in SMA

The implementation of newborn screening (NBS), along with the availability of disease-modifying treatments for spinal muscular atrophy (SMA) has helped bring detection and management of the disorder into the 21st Century. The earlier treatment can be started, even in patients with genetically confirmed SMA but in whom symptoms have not yet appeared, the better the outcomes, according to opinion leaders. They ascribe these improved outcomes to stabilization and rescue of motor neurons.

Investigators from Northwestern University Feinberg School of Medicine and the Ann and Robert H. Lurie Children’s Hospital analyzed the natural history of 21 infants diagnosed and managed at their facility who began disease-modifying therapy within 3 months of delivery. Of these patients, 13 were diagnosed by genetic screening after NBS was implemented in Illinois, five were diagnosed solely by clinical parameters before implementation of NBS in the state, and three were diagnosed prenatally through genetic testing after NBS was introduced in Illinois.

Mean age at the time disease-modifying therapy was first instituted was 28.7 days (11.33 days for those diagnosed prenatally, 24.8 days for those diagnosed with NBS, and 49.4 days for those diagnosed before NBS was implemented in the state; P < .05). Several motor-function measures were obtained at each follow-up visit. SMN2 gene copy numbers did not vary significantly among the stratified cohorts. Nine infants were treated with a single disease-modifying therapy, whereas the remainder received multiple, sequentially or concomitantly.

Based on the results of the CHOP INTEND, TIMPSI, and WHO Motor Milestone surveys, all infants demonstrated gross motor function improvements (near ceiling values in many infants), including SMA-specific and non-SMA-specific norm-referenced assessments. For example, most of the infants in the cohort achieved motor function results from the CHOP INTEND by age 3 months, regardless of SMN2 copy number or how diagnosis was made.

The researchers concluded that “This real-world cohort adds to the evidence that prenatal testing and NBS for SMA is associated with earlier time to first treatment and improved motor outcomes, including the ability for the majority to independently sit and ambulate within typical age ranges.”

They acknowledged that prenatal diagnosis, short durations between positive genetic testing and referral to a specialized SMA treatment center “likely facilitated positive outcomes.” The investigators recommended longer-term investigation with larger patient numbers to further clarify motor function outcomes, as well as barriers to screening, diagnosis, and treatment in this population.

How Meaningful Are Changes in HFMSE Scores for Adults With SMA?

Although the newest treatments for spinal muscular atrophy (SMA) have offered new hope to patients, none are curative. The survey most used to measure changes in motor function, the Hammersmith Functional Motor Scale-Expanded (HFMSE), is also relied upon by the FDA in reviewing new SMA medications for approval. Yet, these motor function scales do not necessarily translate simply into psychosocial well-being as perceived by the patient.

A group of US researchers sought to understand how small motor function changes registered in the HFMSE or no change at all (i.e., stabilization of condition) are viewed by adult patients with SMA in terms of their overall psychosocial health and outlook. They conducted 60-minute, semistructured interviews with 32 patients (mean age, 44.0 yr [range, 18–72 yr]; 72% restricted to sitting, 28% able to walk). Ninety-four percent of the patients were receiving either nusinersen or risdiplam at the time of the interviews.

They collected comments from patients on their perceived impact of worsening (an HFMSE score dropping one point), improvement (score rising one point), or stability for each of the HFMSE motor function components. Therefore, changes in any one component, which may result in a small total score change, may be perceived as having psychological as well as quality-of-life effects that are important to the individual patient.

The investigators found that “adult patients generally regarded clinical meaningfulness as changes or stabilization that affect their physical or emotional health, quality of life, or ability to perform activities of daily living, with even small or gradual changes being potentially meaningful.” They also noted that patients’ perception of functional tests (like HFMSE) may not reflect what is truly meaningful for them, like being able to unbutton a shirt or not feeling as fatigued.

For example, a 49-year-old patient related that a one-point improvement in the supine-to-prone position measure of HFMSE “…would change everything…because you know, when I’m on my back, I’m scared. That’s a scary feeling to not be able to move and be stuck…I think that will boost my mentality up, knowing that I can do it and not worrying about what’s going to happen or have to get somebody to do it for me…It will make a big difference.”

The researchers concluded based on these patient reflections that “any point improvements or stabilization in motor function are seen as meaningful and can be linked to enhanced psychosocial wellbeing.”

Adherence and Persistence to Risdiplam and Nusinersen Therapy in Patients With SMA: A Real-World Study

Risdiplam and nusinersen are effective disease-modifying therapies for spinal muscular atrophy (SMA) that require ongoing administration. Risdiplam is a once-daily oral medication, whereas nusinersen is given in four loading doses intrathecally over 58 days, followed by intrathecal maintenance injections every four months.

Researchers from Novartis Pharmaceuticals retrospectively analyzed long-term treatment patterns and gaps associated with these medications, using 10 years of administrative claims data (nusinersen was first approved in 2017, risdiplam in 2020). The mean age of the patients were 20.3 years (range, 0.7–61.9 yr) in those receiving risdiplam and 17.6 years (range, 0.0–61.1 yr) for those administered nusinersen. In terms of gender, the patient mix was relatively equivalent (53.4% female, 46.6% male in the risdiplam cohort, 51.2% female, 48.8% male in the nusinersen cohort). Between 75.5% and 80.3% of the total population had SMA comorbidities at the time of data collection.

The most common insurance coverages for the study participants were as follows: Medicaid insurance only—46.0% in the risdiplam group, 35.2% in the nusinersen group; Commercial insurance only—25.7% vs. 44.5%, respectively; Multiple insurance coverages—24.6% vs. 18.2%, respectively.

After 12 months of therapy, 70% patients receiving risdiplam persisted with therapy, and this figure dropped after 36 months to 40%. Adherence to risdiplam therapy (measured as ≥ 80% of proportion of days covered) was 74% after 12 months of treatment and 56% after 36 months. For those receiving nusinersen, persistence dropped from 66% after 12 months to 34% after 36 months; adherence was 66% after 12 months and 45% after 36 months.

More than three-quarters of the patients who did not persist with either of these two therapies had at least one claim for another chronic disease-modifying therapy after loss of persistence. According to the researchers, this likely suggests a switch to or re-initiation with other treatments, as patients’ persistence with any chronic disease-modifying therapy was relatively high over 36 months.

They concluded, “These findings indicate that although most patients with SMA continue to use chronic disease-modifying therapies throughout the 36-month follow-up period, more than half demonstrate suboptimal treatment utilization, as evidenced by switching/re-initiation over time and gaps in adequate drug supply.” The researchers recommended further investigation to determine the relationship among the drivers of suboptimal persistence and adherence, including barriers to access, the factors underlying switching behaviors, and reasons for discontinuing therapies.

Prodromal Swallowing Deficits in Presymptomatic Spinal Muscular Atrophy

Swallowing problems in patients with spinal muscular atrophy (SMA) will occur in approximately 15% of patients despite pre symptomatic treatment through the first year of life. The use of disease modifying treatments in these patients does effectively improve swallowing in the majority.

Prodromal neuron loss is hypothesized as a source of swallowing difficulties in SMA. Researchers from the University of Minnesota evaluated the pretreatment swallowing physiology and function to try to confirm the cause.

The researchers studied baseline swallowing integrity in 23 infants (mean age, 19 days) who had been diagnosed with SMA but who were presymptomatic and were being routinely evaluated at four medical centers. All of the infants had at least two copies of the SMN2 gene (39% had 3 copies). All were consuming oral nutrition without reported dysphagia symptoms. Infants who had received disease-modifying therapy were excluded from the investigation.

Upon swallowing studies, the researchers found that 43% of the infants evaluated had reduction in the timing or extent of soft palate closure of the nasopharynx during the swallowing process. Virtually all (91%) of the infants exhibited some penetration of thin liquids into the airway during their videofluoroscopic swallowing studies; this occurred in a median of 19% of all swallows.

Approximately three-quarters of the infants tested required more than 3 sucks before swallowing the liquid (reference, 1—3 sucks/swallow). More than 30% required at least 5 sucks per swallow.

Aspiration of liquids was evident in 30% of the infants tested, despite not demonstrating functional swallowing impairments (and was not dependent on number of SMN2 copies). Opening size of the upper esophageal sphincter was not found to be a factor in more than 90% of the infants tested.

The researchers concluded that these presymptomatic infants with SMA demonstrate problems with the sucking and swallowing mechanism with the first month of life. They believe that this supports prodromal neuron loss as a cause. “Investigations examining the long-term implications of these perturbations are critical to guide clinical care guidelines,” they recommended.

Using Wearable Sensors to Assess Changes in Range of Motion in Patients With SMA

As spinal muscular atrophy (SMA) progresses over time, deterioration in motor neurons and muscle strength results in limited range of motion, which is not objectively captured in clinical scales used to assess the disease. Researchers from Cook Children’s Hospital attempted to more accurately measure patients’ range of motion, utilizing wearable (noninvasive) sensors.

The researchers identified patients with SMA who were receiving treatment through a retrospective database, and enlisted them to wear eight sensors placed throughout the body. A total of 27 patients (age range, 7 days to 18 years) provided motion capture data throughout 18 months, and motion capture was performed in the supine, sitting, and standing positions (according to patients’ capability at the time).

They found they were able to detect clinically significant changes in range of motion in the SMA population, regardless of patient age or therapy being administered. For example, they reported that in the supine position, statistically significant improvements in range of motion through 12 months were revealed for right and left hip abduction (P = .002 and .02, respectively), as well as right plantarflexion (P = .05). They also observed worsening of right elbow flexion (P = .009), and right and left dorsiflexion (P = .03 and .01, respectively).

For patients in the sitting position, they reported the following 6-month improvements: right hip flexion (P = .05) and right knee extension (P = .02). Over 12 months, they saw improvements in left cervical rotation (P = .02) and right shoulder abduction (P = .01). At 18 months, these patients in the sitting position also registered improvements in right shoulder flexion (P = .04) and right shoulder abduction (P = .009).

They concluded that using wearable sensors, healthcare professionals can objectively track patients’ range-of-motion progress over time, and this methodology is “relatively easy and accessible.”

Social Determinants of Health in Adults Living With SMA

Social, demographic, and economic factors have been shown to strongly affect health and well-being for many disorders. Overall, adverse social determinants of health (SDOH) create greater risks of poor health for both individuals and populations.

As adults with spinal muscular atrophy (SMA) frequently utilize multidisciplinary care to optimize their well-being, quality of life, and their lifespan, researchers from multiple US sites sought to understand the SDOH barriers to care in this population.

The researchers analyzed an insurance claims database and identified persons with SMA for whom claims were filed between 2016 and 2024. Claims data were linked to another database containing SDOH information—a portfolio of nonclinical factors that can influence health outcomes. Algorithms were used to estimate “SDOH total risk” levels.

A total of 1,080 records of patients with SMA were deemed eligible for inclusion in the study, based on the continuity of insurance, adequate comorbidity data, and having complete SDOH data. Their mean age was 51 years, 61% were female, and 56% were white. Sixty-two percent were of working age, and 53% had commercial insurance. Their mean Quan-CCI (comorbidity index) score was 1.3.

The study revealed that only 21% lived alone; 79% lived in a household with more than one other adult. Although 93% of the households having vehicles, access to public transportation was lacking in 53%.

In terms of education level, the population cohort roughly matched the US general population for college degree (36%), high school diploma (26%), and no high-school diploma (9%). About 28% of the cohort also attended some college (compared with 16% of the US population). Eighty-five percent lived above the federal poverty level, and one-quarter had an annual income of $50,000 to $74,999. Another 14% earned up to $100,000 and 17% up to $150,000.

The researchers calculated a high SDOH total risk level for 43% of patients, a medium risk level for 22%, and low risk for 35%. High risk levels by SDOH component were: 40% for medication access, 39% for food insecurity, 28% for access to care, and 26% for housing instability. They found a statistically significant association between higher comorbidity index score and high SDOH total risk category (P ≤.001) compared with the lowest risk category. This association was not found to be statistically significant for those at medium overall SDOH risk.

The investigators recommend that “SDOH variables should be carefully considered to support equitable access to care for individuals with SMA.”