December 30, 2025

@michaelokun

Long-Term Tofersen: Could targeting SOD1 change ALS trajectory? Spoiler alert: YES. Antisense oligonucleotide is a short strand of genetic material designed to reduce production of a harmful protein by binding its messenger RNA. Timothy Miller and colleagues describe in a new paper in JAMA Neurology the long-term outcomes of Tofersen in SOD1 amyotrophic lateral sclerosis, integrating the VALOR trial and its open-label extension. Key points: - Earlier initiation of Tofersen was associated w/ less decline in function, breathing, strength and quality of life over about three years of followup. - Neurofilament levels dropped substantially and durably, supporting slowed neurodegeneration. - Survival and time to major disease milestones favored earlier treatment. - Long-term safety signals looked good. My take: This study reinforces a critical principle: hit the target early and stay the course. I like how they are following folks long-term. Biomarkers like neurofilament may one day guide care and accelerate progress. Here are 5 points that resonated w/ me: 1- Earlier treatment mattered and delaying therapy came at a cost. 2- Biomarkers helped to show the treatment was working before clinical changes were fully visible. 3- Some participants stabilized or even improved, which is rare in ALS. 4- Safety issues were largely related to the procedure and were frequently reversible. 5- This approach may open the door for earlier and even presymptomatic intervention in genetic ALS. https://jamanetwork.com/journals/jamaneurology/fullarticle/2843130 #ALS #michaelokun #fixelinstitute