Introduction/Aims
There is limited information on the potential effects of repeated intrathecal antisense oligonucleotide drug delivery on cerebrospinal fluid (CSF) biochemical and blood cell profiles. This study aimed to examine longitudinal changes in the biochemical components (glucose, protein) and blood cell counts in the CSF of spinal muscular atrophy (SMA) patients treated with intrathecal nusinersen.
Methods
We collected and analyzed clinical and CSF parameters (cell count, protein, glucose, culture) of 50 individuals with SMA during nusinersen treatment (22 type 1, 17 type 2, and 11 type 3).
Results
The median protein concentration at baseline and during treatment was within the normal range but rose during treatment and was significantly above baseline at the time of the ninth intrathecal injection (p = 0.02, two‐tailed Wilcoxon matched‐pairs test, and p = 0.0015, Friedman test for repeated measures). Further analysis showed that the increase in CSF protein concentration was evident for SMA types 2 and 3 patients, but not for type 1. This observation was also demonstrated by a significant correlation between the SMN2 gene copy number and the increase in CSF protein concentration (Spearman rank correlation test).
Discussion
Our results demonstrate that a delayed increase in CSF protein concentration is expected during nusinersen treatment for SMA types 2 and 3. This might reflect the medication's effect and a possible therapeutic biochemical marker.
Neuromuscular Disorders 31 (2021) S47-S162(n = 1). The majority of patients (90/148 [61.6%]) had 2 copies of the SMN2 gene; 1 (0.7%), 42 (28.8%), 12 (8.2%), and 1 (0.7%) had 1, 3, 4, and > 4 copies of SMN2 , respectively; 2 patients had unknown copy number. The majority of patients (56.1%) had < 12 months of follow-up. Of 17 patients with 2 or more motor milestone assessments, 7 maintained milestones and 9 achieved new milestones. Adverse event (AE) data were reported for 144 of the 148 patients with known treatment regimens (97.3%); 75 (52.1%) reported at least 1 treatment-emergent AE; 34 (23.6%) reported at least 1 serious AE (12 [8.3%] related to OA treatment). Safety and effectiveness will be presented by treatment regimen. The RESTORE registry provides extended real-world assessments of patient outcomes and SMA interventions gleaned from routine clinical practice. The majority of patients with assessments of motor milestones demonstrated improvement over the follow-up period. Based on data available to date, the AE experience of OA observed in RESTORE is consistent with experience previously described for SMA; no new safety signals were identified in patients treated with OA or in those who switched to OA from prior treatment.
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