Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in SOD1 make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of SOD1 mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.
Keywords: MRNA degradation; SOD1; amyotrophic lateral sclerosis; antisense oligonucleotide; edaravone; riluzole; sodium phenylbutyrate-taurursodiol; tofersen.
What is this summary about? Amyotrophic lateral sclerosis is a fatal, progressive disease of the motor system. Most approved treatments have a modest effect on disease progression. Tofersen is a recently approved medication that acts by reducing a toxic protein found in a particular form of inherited amyotrophic lateral sclerosis. This is an overview of the published clinical data for tofersen as well as some background information about tofersen and other treatments for amyotrophic lateral sclerosis.What were the results? Treatment with tofersen reduced levels of the target protein and markers of nervous system damage. In longer follow-up, patients treated with tofersen showed less disease progression.What do the results of the study mean? Treatment with tofersen likely slows progression in this form of inherited ALS, though longer duration studies would likely be needed to demonstrate this effect.