FDA Approves Higher Dose Nusinersen, Fatigue, EDS Uncorrelated with OSA, Shifting Neurologic Research in Down Syndrome

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Welcome to the Neurology News Network. My name is Louie Pasculli. Here’s a look at this week’s top stories in neurology.

Beginning with FDA news, nearly 10 years after its original approval, the FDA has approved a new higher dose strength for nusinersen (Spinraza; Biogen) as a treatment for patients with spinal muscular atrophy (SMA). This new dosing regimen, which is comprised of 50 mg/5 mL and 28 mg/5 mL doses, is designed to deliver a higher concentration of drug through both the loading and maintenance dosing phases, leading to more efficacious results for patients with the disease.¹

The high-dose regimen of nusinersen, expected to become available in the coming weeks, introduces a faster loading schedule for treatment-naïve patients. This approach includes two 50 mg doses given 14 days apart, followed by ongoing maintenance injections of 28 mg every four months. For patients switching from the low-dose regimen, treatment would continue on the same four-month dosing interval after completing a single high-dose loading phase.

The US FDA approval of high dose nusinersen, which comes months after the European Comission granted greenlight, is backed by the phase 2/3 DEVOTE study (NCT04089566). This global, 3-part trial was designed to test safety, pharmacokinetics, and efficacy of this new regimen compared with the originally approved 12 mg regimen. All told, results from the study showed statistically significant improvements in motor function, as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), when compared to a prespecified matched sham (untreated) group from the ENDEAR study (mean difference: 26.19 points; +15.1 vs. -11.1, P <0.0001).

Transitioning to sleep disorders, A recently published cross-sectional study reported that fatigue, measured by Fatigue Severity Scale (FSS), and objective excessive daytime sleepiness (EDS), measured by the mean sleep latency (MSL) on the multiple sleep latency test (MSLT), were uncorrelated in patients with obstructive sleep apnea (OSA). However, the findings, published in Sleep Medicine, showed that each OSA symptom contributed similarly to subjective EDS.²

Using a cohort of 603 patients from the US and Germany, findings showed that the MSL was not correlated with the FSS overall (r = −.008, P = .85) or by each site. In contrast, results revealed that the FSS and the Epworth Sleepiness Scale (ESS) demonstrated a mild correlation (r = .28, P <.001), with slightly higher correlation in the US cohort (r = .38) compared with the German cohort (r = .25). In addition, authors noted that the ESS and MSL were modestly inversely correlated (r = −.23, P <.001).

“Our finding that subjective EDS is a mix of EDS and fatigue is important for a different reason. We have demonstrated that even if one could reduce the variability of ESS by, for instance, computing a sample mean ESS over a population of patients with OSA, the information in that sample mean about symptoms of OSA would still be an uninterpretable mix of information about two uncorrelated symptoms, objective EDS and fatigue,” senior author Avram R. Gold, MD, associate professor of medicine at the Stony Brook University Sleep Disorders Center, and colleagues wrote.²

Switching gears, down syndrome, caused by trisomy 21, is the most common chromosomal condition associated with intellectual disability, affecting approximately 1 in 700 live births in the United States.1 Improvements in medical care over the past several decades have led to a steady increase in life expectancy, with many individuals now living well into adulthood. As a result, the clinical landscape of Down syndrome has shifted, with neurologists increasingly encountering age-related neurological considerations in this growing population.

Alongside these demographic changes, there has been a renewed focus on better understanding the neurological profile of Down syndrome across the lifespan, including how underlying biology may influence later-life cognitive outcomes. Ongoing research efforts have begun to reshape how clinicians think about disease risk, monitoring, and long-term care in this population, setting the stage for a deeper exploration of the relationship between Down syndrome and neurodegeneration.

To read the full piece and to get more direct access to expert insight, head to NeurologyLive.com. Be sure to tune in next week to stay up to date on the latest in neurology. I’m Louie Pasculli, thanks for watching Neurology News Network.

REFERENCES
1. FDA Approves New High Dose Regimen of SPINRAZA® (nusinersen) for Spinal Muscular Atrophy. News release. Biogen. March 30, 2026. Accessed March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/fda-approves-new-high-dose-regimen-spinrazar-nusinersen-spinal
2. Gold MS, Stoohs RA, Gold AR. Objective versus subjective excessive daytime sleepiness in OSA: Quantifying the impact of fatigue. Sleep Med. Published online February 25, 2026. doi:10.1016/j.sleep.2026.108867