Older Ventilated Children with SMA See Improvements After Gene Therapy

Research has shown that Infants with spinal muscular atrophy (SMA) who receive a gene therapy in the first year of life can typically avoid permanent ventilation. Less is known about how the disease-modifying treatment affects older children. Now, a new study shows that patients who get the treatment at 2 years old or later can still greatly benefit.

The study, published in Advances in Respiratory Medicine, followed 22 patients with SMA who were on long-term ventilation via tracheostomy before receiving Zolgensma (onasemnogene abeparvovec) at a median age of 26 months. Such children are typically excluded from SMA gene therapy trials. In this study, they showed significant improvements in respiratory function over a mean follow-up period of 7.6 months.

The research, led by Mohammad Ala' Alajjuri of the College of Medicine, University of Sharjah, United Arab Emirates, found a meaningful reduction in the number of patients experiencing paradoxical breathing, where the patient’s weakened muscles cause the diaphragm to work harder than the chest muscles, resulting in the chest moving inward instead of outward during inhalation. This condition causes poor oxygen intake and can lead to respiratory complications.

Among 18 patients assessed for paradoxical breathing, 72% (13) had the condition prior to receiving gene therapy, compared to 22% (4) who still had it after treatment. The gene therapy also helped study participants improve their ability to cough, a critical factor that can both prevent hospitalizations and decreases hospital stays due to respiratory infections.

“Gene therapy was effective at a late age of administration, indicating that older patients with SMA-1 still have a chance for improvement if presented late for the therapy,” the study authors wrote. Although prior research indicated gene therapy would not lower the amount of time children spend on ventilator support, this study showed that “11 patients had reduced hours on ventilation, and one patient was completely weaned off the ventilator eight months after gene therapy.”

Prior to receiving gene therapy, the patients in the study underwent intensive assessment and management at long-term ventilator clinics, which helped them build up tolerance to safely be off ventilation at least eight hours a day. The study authors suggest this pretreatment approach can accentuate the benefits of gene therapy among SMA patients.

"In conjunction with gene therapy, rigorous, high-quality clinical care is beneficial and should be paired with gene therapy management," the authors wrote.