Gene therapy has transformed respiratory outcomes in spinal muscular atrophy (SMA) type 1, but children still need ongoing lung function and sleep monitoring, according to Moshe Prero, MD, pediatric pulmonologist and sleep medicine physician at University Hospitals (UH) Rainbow Babies and Children’s Hospital.¹
The US Food and Drug Administration (FDA) approved onasemnogene abeparvovec-xioi (Zolgensma) in May 2019 for children aged < 2 years with SMA.2 The approval was based on motor milestone gains, including sitting without support, compared with natural history.² In December 2023, the agency approved exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) for patients aged ≥ 12 years with sickle cell disease (SCD) and recurrent vaso-occlusive events.³,4, 5
At the CHEST 2026 Annual Meeting in Phoenix, Prero presented the session, “Updates in Pediatric Pulmonology: Year in Review,” which addressed the pulmonary implications of these therapies alongside bronchopulmonary dysplasia and chronic mechanical ventilation.¹ HCPLive spoke with Prero during the meeting.
“Gene therapy has revolutionized the disease process for these patients,” he said. “Now, I’m seeing patients who are walking around without any ventilatory needs.”
Respiratory Outcomes After Gene Therapy in SMA Type 1
Prero noted children with the most severe form of SMA, often labeled type 1 SMA, were historically described in the neurological literature as “non-sitters.” These patients never developed the motor strength to sit independently.
Before gene therapy, they typically required ventilatory support through a mask or a tracheostomy tube during the first year of life and nearly always by the second year. Prero now sees patients from this population who sit, walk around the exam room, and participate in society as ambulatory children.
“It’s changed the landscape entirely,” Prero said.
Long-term outcomes remain uncertain. According to Prero, the residual disease burden after gene therapy is not yet defined, nor is its effect on sleep and respiratory needs as these children age.
Some patients may eventually need nocturnal continuous positive airway pressure (CPAP), and others may develop swallowing dysfunction or scoliosis, each of which carries respiratory consequences. Prero said further research is needed to characterize these trajectories.
Monitoring Lung Function and Sleep-Disordered Breathing After Gene Therapy
Because individual responses to gene therapy vary, Prero recommended pulmonologists continue structured follow-up even when motor function improves. Spirometry and pulmonary function testing should begin once a child is old enough to complete them reliably.
Screening for sleep-disordered breathing is equally important, Prero added. He advised clinicians to ask about nighttime snoring and about subtle daytime clues, including morning headaches, mood or behavior changes, and changes in concentration.
“If the patient screens positive ... meaning they have snoring and they have those changes during the day, it’s important to get a sleep study,” Prero said.
For SCD, Prero said disease-modifying therapy does not yet change the approach to acute chest syndrome. In his view, patients who develop acute chest syndrome after receiving such therapy should be managed according to the existing standard of care.
References
Prero M. Updates in pediatric pulmonology: year in review. Presented at: CHEST 2026 Annual Meeting; October 21, 2026; Phoenix, AZ.
Exagamglogene autotemcel: MedlinePlus Drug Information. Medlineplus.gov. 2024. Accessed October 27, 2026. https://medlineplus.gov/druginfo/meds/a624018.html
Lovotibeglogene autotemcel Injection: MedlinePlus Drug Information. Medlineplus.gov. 2024. Accessed October 27, 2026. https://medlineplus.gov/druginfo/meds/a624020.html
