Dr Sean Smith | Fighting ALS at the Genetic Level: Real World Results for Tofersen

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Dr Sean Smith | Fighting ALS at the Genetic Level: Real World Results for Tofersen

Sep 16, 2025 | health and medicine

About this episode

Amyotrophic lateral sclerosis (or ALS), also known as Motor Neuron Disease, is a devastating condition that gradually reduces a patient’s ability to move, speak, and ultimately breathe. Among the various forms of ALS, about 2% of cases are linked to a mutation in a gene called SOD1. For years, there has been no effective treatment for these patients. A new investigation conducted by Dr. Sean Smith and his colleagues at Washington University in St. Louis offers new hope for ALS patients.

In their recent study, the researchers explored the real-world use of a drug called Tofersen, a genetically targeted therapy designed specifically for people with SOD1-related ALS. Tofersen works by using tiny snippets of synthetic genetic material to block the faulty genetic instructions that cause a toxic buildup of the mutant SOD1 protein in the body – a major contributor to the disease.

In clinical trials, Tofersen had already shown promise, and the FDA granted it accelerated approval in 2023. But what happens outside the controlled environment of a clinical trial?

To find out, Dr. Smith’s study followed seven patients with SOD1 ALS who received Tofersen treatment. The results were compelling. Patients showed not just a slowing of disease progression, but in some cases, actual improvements in function. On average, there was a marked drop in levels of neurofilaments, proteins released when motor nerves are damaged. This suggested that the drug was successfully protecting neurons.

One of the key takeaways from Dr. Smith’s research is that this group of patients were able to maintain their independence longer than expected. Some patients showed improvements in functional measures, such as improvement in walking speed and the ability to stand up from a chair without assistance – changes that can make a world of difference in daily life.

The safety profile of Tofersen was also encouraging. While some patients experienced side effects like muscle aches or headaches, these were generally mild and manageable with common over-the-counter medications.

Dr. Smith and his colleagues caution that these are early findings from a small group, but they emphasize the significance of their results. Tofersen appeared to produce stability, and even improvement, in a disease known for its relentless progression. As research continues, including long-term studies and efforts to test the drug in other people, like those with early or even pre-symptomatic disease, the landscape of ALS treatment is beginning to shift.

Thanks to the efforts of dedicated researchers such as Dr. Sean Smith and colleagues, patients and families now have a reason to hope.

Original Article Reference:

Summary of the paper ‘Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real-world” setting’, in Annals of Clinical and Translational Neurology, doi.org/10.1002/acn3.52264