Promising advances in spinal muscular atrophy (SMA) biomarkers include neurofilament level as a sensitive indicator of disease activity and treatment response, as discussed at Cure SMA 2026. The meeting also featured a discussion on single-gene noninvasive prenatal testing (NIPT), an emerging prenatal screening tool that may support earlier diagnosis and future in utero treatment strategies.

Following these presentations, featured expert Kapil Arya, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Sandra Ramadani, PhD. Clinical perspectives from Dr Arya on these findings are presented here.

The primary biomarker in SMA is the SMN2 copy number; however, much of the current clinical focus is on neurofilaments. Neurofilament proteins are structural components of the axons that are released during neurodegeneration, and they are measurable in the cerebrospinal fluid and blood. And we now have advanced assays to detect neurofilament at the femtogram level, which makes it a sensitive biomarker.

We have found that neurofilament levels correlate with disease activity and treatment response in SMA and other neurodegenerative diseases. In nusinersen trials, for example, patients with SMA who were treated with this drug had rapid sustained neurofilament decline that correlated with motor function improvement. We now know that after gene therapy infusion, neurofilament levels increase for a certain period, probably due to cellular stress, but then eventually decline with effective treatment. The belief is that monitoring a patient’s neurofilament levels longitudinally can help guide clinical decisions and assess treatment efficacy. A caveat, of course, is that neurofilament levels vary with age. They are high in infancy, decrease in adulthood, and increase again with aging. So, neurofilament level should not be used as the gold standard but should instead be integrated alongside clinical and electrophysiological data, such as compound muscle action potential.

Only a small number of clinicians routinely use neurofilament testing, but I think that more data will convince the community to use it when making treatment decisions. This is where the field is going, and this is where I will be making changes in my practice. Compared with where we were 10 years ago, we are light-years ahead. We can now reliably tell our patients, “We can help you,” and I am hopeful that, with more research, our treatment protocol will be refined even further. This is where more studies and real-world data are needed.

Many open questions remain. How do we interpret transient neurofilament increases post gene therapy? Do we add interventions on that basis? What is the correlation between neurofilament and electrophysiological measures such as compound muscle action potential? How do we care for patients with persistent neurofilament elevation despite treatment? How do we counsel patients about neurofilament testing, and how do we best integrate this into routine SMA care?

At Cure SMA 2026, data presented by Crystal M. Proud, MD, were very impactful (abstract 17). Dr Proud and colleagues found that when presymptomatic infants were treated early, there could be an almost 95% reduction in plasma neurofilament levels. This could be an important biomarker for disease activity even before symptoms start because the dropping neurofilament levels moderately correlate with an improvement in motor function. Monitoring neurofilament levels can also help clinicians verify whether the patient is receiving an optimal dose or whether the treatment protocol needs adjustment. Of note, this research group mentioned that the European Medicines Agency (EMA) has issued a letter of support for neurofilament level as a viable biomarker in SMA and other pediatric neurological diseases, so that is all very promising.

Also at Cure SMA 2026, Karlla W. Brigatti, MS, CGC, gave a presentation on single-gene NIPT for the earlier diagnosis of SMA and the optimized treatment of newborns with infantile-onset SMA (abstract 18). Single-gene NIPT is such a wonderful new screening tool. Of course, this testing is done only after carrier testing is done. If a pregnant female patient is identified as a carrier, only then is single-gene NIPT performed. Cell-free DNA is taken from maternal blood and then tested to see whether the pathogenic variant was inherited by the fetus. After the variant is detected or a patient screens positive, more invasive procedures such as chorionic villus sampling or amniocentesis are done to make the diagnosis.

At the moment, only a minority of patients get single-gene NIPT, and that minority includes families who already know that they are carriers. For example, they have children with SMA and want to determine whether their next pregnancy will carry a risk. Most of the single-gene NIPT I have seen done has been in this cohort. I do not think that the general public, maternal fetal medicine physicians, or obstetrics and gynecology physicians are testing for this, which I would say is fine. We already have newborn screening that detects SMA quite early, and the higher SMA risk is primarily only found in the small cohort of people who already have family members who suffer from SMA.

However, this will be more important in the future. During a Cure SMA 2026 neurodevelopment panel session moderated by Lyndsay Murray, PhD, anecdotal data from 9 pregnant female patients with SMA who were being treated in utero with risdiplam reported promising results without any significant problems. This kind of testing may be the future of detecting and treating SMA in utero because, after all, we know that the degeneration of motor neurons does not start at birth. The earlier we treat, the better the results.