Upper limb motor function improved or stabilized in most children with spinal muscular atrophy (SMA) types 2 or 3 following treatment with nusinersen, according to study results published in the Orphanet Journal of Rare Diseases.
The rare neuromuscular disorder, SMA, is characterized by progressive muscle weakness caused by a homozygous deletion in the survival motor neuron 1 (SMN1) gene. This results in the synthesis of dysfunctional SMN proteins, leading to the deterioration of motor neurons.
The SMN2 gene produces functional SMN proteins. Patients with higher number of SMN2 gene copies exhibit less severe disease manifestations. Nusinersen is an antisense oligonucleotide treatment designed for patients with SMA. It targets the intronic splicing silencer of the SMN2 gene, increasing production of functional SMN protein.
Researchers conducted a prospective, multicenter study (SMArtCARE) consisting of 58 participating medical centers throughout Germany, Austria, and Switzerland. They analyzed data obtained from the SMArtCARE patient registry on 256 children who are nonambulatory with SMA types 2 or 3 treated with nusinersen before reaching 18 years of age. The follow-up period of the study lasted 38 months.
The researchers assessed the impact of nusinersen on upper extremity motor function in these children as evaluated by the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM).
Upper extremity motor function improved in children with SMA types 2 or 3 with 32.4% and 24.6% demonstrating clinically meaningful improvements on the RULM and HFMSE, respectively.
The researchers observed that no motor milestones in upper limb function were lost. Additionally, 8.6% of the children achieved a new motor milestone after nusinersen treatment.
Very small percentages of the children demonstrated decreased upper limb function according to HFMSE (4.3% of patients) and RULM (1.2% of patients) scores.
“Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment,” the researchers stated. They concluded, “Changes were most evident in upper limb function and were observed continuously over the follow-up period.”
Study limitations included missing data points for some patients at certain time points and the difference in quality of data using a registry compared with a controlled clinical trial, although physical therapists and others rating the HFMSE and RULM scoring received regular training to ensure interrater reliability.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Pechmann A, Behrens M, Dörnbrack K, et al. Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study. Orphanet J Rare Dis. Published online October 23, 2022. doi:10.1186/s13023-022-02547-8