Antisense Oligonucleotide Tofersen Distribution in the Central Nervous System of -ALS Autopsy Tissue Donors

What is the biodistribution of tofersen and its impact on SOD1 levels in human central nervous system tissues?In this autopsy case series study of individuals with –amyotrophic lateral sclerosis (-ALS) who received tofersen, recent treatment was associated with therapeutic drug levels in somatic motor systems tissues, ubiquitous transduction of residual somatic motor neurons, and reductions in lumbar spinal cord protein levels ranging from 45% to 84% despite not having been administered 1 to 2 scheduled doses before autopsy. Leptomeningeal and perivascular lymphocytic infiltrates may be an immune response to tofersen related to the common clinical finding of cerebrospinal fluid pleocytosis.The first emerging autopsy tissue data from this case series confirm the predicted distribution of tofersen and robust SOD1 protein reduction in human tissue.

Corresponding Author: Edward D. Plowey, MD, PhD, Biogen, 225 Binney St, Cambridge, MA 02142 (ed.plowey@biogen.com).

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