To investigate long-term changes in motor function in children with SMA, who received gene therapy and to examine the relationship between these changes and the occurrence of orthopedic complications.
The subjects were ten children with SMA (five girls) who received gene and physical therapies at our hospital between February 2019 and August 2024. Their ages ranged from 2–6.1 years (median: 4.5 years). Motor function was assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and Hammersmith Functional Motor Scale-Expanded (HFMSE). Children who received drug treatment prior to gene therapy were evaluated before treatment. This was followed by assessments at baseline (BL), before gene therapy, and at 1, 2, 3, and 4 years after BL. The WHO Motor Milestones（WHO） were confirmed at the final evaluation. Orthopedic complications, including scoliosis and hip dislocation, were assessed using radiography and the Cobb angle (CA), with scoliosis defined as CA greater than 15 °.ned as CA greater than 15 °.
Four children had two copies of the SMN2, five had three copies, and one had a point mutation, with one copy of SMN1 and three copies of SMN2. The ages at SMA diagnosis ranged from 0–12 months (median:2.5 months). Gene therapy was administered between the ages of 3 and 23 months (median:8.5 months). Before gene therapy, seven children received Nusinersen 1–9 doses and one received Risdiplam for a month. The CHOP INTEND scores were 3–46 (median:18) before treatment, 5–62 (median:42.5) at BL, 45–64 (median:54) after one year, 51–64 (median:55.5) after two years, 52–64 (median:60) after three years, and 50–64 (median:58) after four years. HFMSE scores were unavailable, 2–6 (median:4), 2–34 (median:9.5), 8–53 (median:15.5), 13–62 (median:28), and 12–65 (median:33). WHO indicated two children walking, two standing with support, one crawling, four sitting, and one child with no acquisition. Scoliosis was observed in six children, two with a CA of 50 ° or more indicating the need for surgery. Hip dislocation was observed on one side in two children.
All children showed improvements in motor function following gene therapy; however, more than half of them exhibited scoliosis. Except for one child who achieved a perfect CHOP INTEND score, the others demonstrated a considerable increase in their score immediately after treatment, followed by stabilization without reaching maximum scores. This pattern reflects the characteristic central-predominant muscle weakness associated with SMA, likely influencing the development of orthopedic complications, such as scoliosis and hip dislocation.
This study provides valuable insights detailing the long-term changes in motor function following gene therapy in clinical practice. It further provides a basis for physical therapy in setting goals for motor function and preventing orthopedic complications.
gene therapy
motor function
