Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases

Abstract

Abstract 5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are two distinct neurological disorders leading to degeneration of lower motor neurons. The antisense oligonucleotides (ASOs) nusinersen and tofersen are novel disease-modifying agents for these diseases, respectively. In the context of ASO treatment, the cytological characteristics and composition of cerebrospinal fluid (CSF) have recently garnered particular interest. This report presents a case series of CSF cytology findings in two patients with SMA and ALS revealing comparable unspecified macrophage inclusions following treatment initiation with nusinersen and tofersen. Yet, the presence of these “asophages” in the treatment course of two different ASOs is of unclear significance. While both treatments have been well tolerated, this phenomenon warrants attention, given the long-term nature of these treatments.

Keywords

• ALS
• SOD1
• SMA
• Antisense oligonucleotide therapy
• Nusinersen
• Tofersen