Tofersen for the treatment of amyotrophic lateral sclerosis caused by mutations in the SOD1 gene

Tofersen (BIIB067) is in clinical development for the treatment of amyotrophic lateral sclerosis (ALS – also known as motor neurone disease) caused by mutations in the SOD1 gene (SOD1-ALS). ALS is a progressive disease of the nervous system, where nerve cells in the brain and spinal cord that control voluntary movement gradually deteriorate, causing loss of muscle function and paralysis. ALS is a debilitating and life-threatening disease. The gradual loss of neurons leads to a paralysing effect on muscles used for breathing, which usually leads to death from respiratory failure.
Tofersen is designed to help some patients with ALS who have a change in the gene responsible for producing the enzyme SOD1. Mutations in the SOD1 gene confer a new toxic property to the SOD1 protein, though exactly how disease-associated SOD1 is toxic to neurons is unknown. Tofersen is made of a small strand of synthetic genetic material that prevents translation of SOD1. By reducing the amount of both normal and defective SOD1, tofersen is expected to improve the progression of SOD1-ALS. Tofersen is given as an intrathecal injection and if licensed, it will offer a treatment option for patients with SOD1-ALS who currently have very limited available options.