Alternative Method of Nusinersen Administration Identified for SMA Cases With Spinal Deformities

Unilateral interlaminar fenestration (UILF) on the convex side has been observed as an effective method for the administration of nusinersen in patients with spinal muscular atrophy (SMA) also enduring severe scoliosis, according to a recent study published in Orphanet Journal of Rare Diseases.

Skeletal deformities are a common occurrence in SMA, with over 60% of patients developing scoliosis that can progress severely. Spinal deformities in particular often require surgical corrections such as posterior spinal fusion (PSF). Although these interventions can improve the quality of life for patients with SMA, PSF causes osseous fusion that hinders intrathecal access. This access is necessary for the application of the novel gene therapy, nusinersen.

Lumbar Region Model | image credit: Crystal light - stock.adobe.com

Nusinersen is an antisense oligonucleotide that has showcased great benefits for prolonging life expectancy and slowing disease progression across all forms of SMA. This drug, however, cannot penetrate the blood-brain barrier and, therefore, intrathecal injection is the standard, intended method for its application. Despite innovations such as the intrathecal catheter, which comes with its own risks, intrathecal administration of nusinersen in patients with SMA and severe spinal deformities needing spinal fusions has remained difficult. To address this challenge, researchers conducted a study to evaluate the safety and efficacy of UILF on the convex side for administering nusinersen in this patient population.

From January 2020 to October 2021, the medical record of patients with SMA who underwent PSF and UILF were retrospectively reviewed. Included patients each had follow-up for at least 1 year following their surgery. Thirteen patients with SMA were enrolled (10 SMA type II, 3 type III).

UILF was solely performed on the convex side in an area of approximately 15 mm x 20 mm. In 11 patients, distal fusion to the pelvis occurred; as for the remaining 2, L5 was identified as the lowest instrumented vertebrae. Ultrasound scanning was used for guided puncture in the patients’ lumbar region. At the L2-L3 level, 6 patients received fenestration; the remaining 7 patients had L3-L4 chosen for windowing. Clinicians used a 22 gauge, 10-cm echogenic needle with a stylet and short-bevel tip during the ultra-sound guided process. Upon removal of the stylet, 5 mL of cerebrospinal fluid was retrieved for additional evaluation while an equal amount of nusinersen (5 mL/12 mL) was administered.

In total, 9 patients were given intrathecal nusinersen through lumbar puncture. Throughout the 1-year follow-up, injections of nusinersen were received between 4 and 9 times per patient, with an accumulative total of 50 administrations. During this time, each injection was successfully completed with the aid of ultrasound and no severe complications were reported following administration. Some minor complications were reported by 4 patients, including headache and vertigo, but these symptoms were quickly resolved.

Among the limitations the author noted were the small sample size of their cohort, the shorter length of follow-up, and lacking comparisons between patients treated with UILF and those with intrathecal catheters. While their findings promote the safety and efficacy of this form of lumbar puncture, the authors conclude by advocating future research take on larger samples, longer follow-up, and a determined control group to bolster the results they observed.

Reference

Wang Z, Feng E, Jiao Y, et al. Unilateral interlaminar fenestration on the convex side provides a reliable access for intrathecal administration of nusinersen in spinal muscular atrophy: a retrospective study. Orphanet J Rare Dis. 2023 Nov 29;18(1):369. doi: 10.1186/s13023-023-02972-3