03:45 PM Abstract No. 204 an Institutional Experience of Intrathecal Spinraza (nusinersin) Injection for Spinal Muscular Atrophy in Adult Patients with Respiratory Dysfunction

Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder secondary to dysfunction of survival motor neuron (SMN) protein characterized by the degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem resulting in progressive muscle atrophy and weakness. Until recently, management consisted of supportive care aimed at reducing associated comorbidities, such as respiratory failure. In 2016, the FDA approved intrathecal Spinraza (nusinersin, Lexicomp, USA), an antisense oligonucleotide that splices into the typically dysfunctional SMN2 gene, for the treatment of SMA after interim statistical report from the multicenter ENDEAR trial. The trial showed improved progression to motor milestones, increased the likelihood of event free survival, and increased likelihood of overall survival for infants with SMA [1]. We currently administer Spinraza at our institution to adult patients with SMA and respiratory dysfunction as part of a multi-disciplinary approach to improve respiratory function in the hopes of reducing respiratory failure and increasing survival. Retrospective analysis of 17 patients (median age 33 years, range 19-64 years; male 9, female 8) with SMA and baseline respiratory dysfunction at different points of our Spinraza regimen. Negative inspiratory force (NIF) and vital capacity (VC) were compared to baseline after each Spinraza injection. Spinraza injection regimen as follows: injection q2weeks x 3 followed by injection 4weeks later and q12weeks maintenance. Mean improvement from baseline NIF/VC for current patients after each Spinraza injection as follows: n=17 at 2 weeks 32.79%/23.12% (SD 111.85%/62.06%); n=17 at 4 weeks 50.43%/19.47% (SD 75.87%/73.85%); n=13 at 6 weeks 94.23%/15.94% (SD 150.38%/62.91%); n=7 at 10 weeks 149.54%/4.52% (SD 182.28%/32.98%); n=4 at 22 weeks 181.02%/36.15% (SD 164.63%/109.89%). Our institutional experience shows variable, but overall, improvement of respiratory function in adult SMA patients receiving Spinraza injections at the time of initial data collection.