NeuroVoices: Jinsy Andrews, MD, on Prodromal ALS, Emerging Biomarkers, and the Next Wave of Targeted Therapies

Amyotrophic lateral sclerosis (ALS) remains one of the most challenging neurodegenerative diseases to treat, with no broadly approved disease-modifying therapy and a long road ahead for the field. In recent years, however, meaningful progress has been made, with emerging therapies and biomarker-driven research beginning to shift what is possible. Among the most significant developments has been the conditional approval of tofersen (Qalsody; Biogen) for SOD1-associated ALS, which opened the door for antisense oligonucleotide technology and accelerated approval pathways to be applied more broadly across genetic subtypes.

Jinsy A. Andrews, MD, was among the featured speakers at NYU Langone's Brain Health Media Roundtable, where leading experts across neurology, neurosurgery, ophthalmology, and neuropsychology gathered to discuss the science and real-world implications of brain health today. As Director of the ALS Clinic and Director of Clinical Trials at NYU Langone Health, Andrews brings a rare combination of clinical, research, and advocacy expertise to the conversation. She also serves as elected co-chair of the Network of Excellence for ALS (NEALS) and was instrumental in the passage of the ACT for ALS Act, signed into law in 2021.

Following the event, NeurologyLive caught up with Andrews to discuss her thoughts on the roundtable and some of the clinical takeaways. As part of a new iteration of NeuroVoices, Andrews addressed where ALS drug development stands today, what the pipeline looks like heading into 2026, and how conversations around prodromal ALS are evolving. Furthermore, she also weighed in on which biomarkers beyond neurofilament light chain are poised to play a larger role in the years ahead.

NeurologyLive: What were your first thoughts on the event today?

Jinsy A. Andrews, MD: I think it was really great that NYU was able to host a brain health roundtable. There's so much going on in general for brain health, and so many key variables that anyone healthy today can act on to keep themselves healthy and cognitively sharp, including lifestyle factors like eating a good diet, exercising, and getting enough sleep. These are simple things that are in our court to take care of ourselves, so that our minds can be healthy and we can prevent things like Alzheimer's or other neurodegenerative diseases in the future.

What are some of the research steps we as a community need to continue to take so that we hopefully get disease-modifying treatments in the coming years?

I think tofersen was essentially a game changer for the field, and I think everybody knows that, because it received conditional approval based on a biomarker that we really needed in ALS, though we're still understanding how that biomarker moves and changes over time in sporadic ALS. Tofersen was approved for SOD1-specific ALS, which is only one to two percent of all ALS, but understanding that biomarker also leads us toward developing therapies that could potentially be considered for accelerated approval in the future. It also provided an opportunity to use antisense oligonucleotides, or ASOs, as potential targets for other gene therapies.

Coming down the pipeline for 2026, we will get a readout for the FUS gene-targeted ASO being developed by Ionis in partnership with Otsuka. We're also going to learn about treating presymptomatic individuals who carry the SOD1 gene in a study called ATLAS, where we are following neurofilament levels and trying to treat patients before they develop ALS to prevent it or delay its onset. These are new frontiers coming down the pipeline for ALS.

How have conversations changed in the ALS field around treating the disease in that prodromal phase, and how are researchers thinking about getting even earlier in that window?

I think that's the next frontier, and we're really getting into it now. Looking at individuals who carry a gene mutation but don't yet have any ALS symptoms is a key area of focus in the field right now. There have been a lot of nonprofit organizations, like End the Legacy, thinking about ways to have clinics care for people at risk for ALS. There's also All ALS, a natural history study that has been launched to study not only symptomatic individuals with ALS, but also people who are at risk, to better understand where that prodromal phase is and which biomarkers might signal that someone is going to convert to ALS.

Beyond that, we're thinking about what we can do, if someone is at risk, to prevent ALS from happening at all. It's not just about the drugs. It might be environmental risk factors that can be avoided, or lifestyle factors like exercise, mental activity, and social engagement. As the chair of NEALS, I can share that our annual meeting in October 2026 will have a major focus on this, and this is actually news. We'll be opening with an entire panel dedicated to at-risk individuals and how to navigate that phase of ALS.

We've talked so much about biomarkers, and neurofilament light is clearly the big one right now in the field. Which other biomarkers do you foresee taking the next step over the next year or so?

Everyone has been fairly fixed on neurofilament, but I think one of the things that could be huge for the future involves the scientific and lab-based community studying cryptic exons, and specifically markers related to TDP-43. This protein is particularly critical because it's not only implicated in genetic forms of ALS, but also in sporadic forms, and it's thought to be toxic when it accumulates and misfolds in motor neurons. There are many targeted therapies currently being evaluated as investigational products for ALS, and having that key biomarker could really help lead us to success in the future.