by Raphael Wurm
Each month the eanNews editorial team reviews the scientific press for recently published papers of outstanding interest to neurologists. Below we present our selection for January 2026.
For our Paper of the Month, go here: Research Paper of the Month: Medical Management and Revascularization for Asymptomatic Carotid Stenosis – eanNews
OX2R Agonist Oveporexton Improves Cognitive Symptoms in Narcolepsy Type 1
A secondary analysis of a phase 2 randomised clinical trial (TAK-861-2001) evaluated the effects of oveporexton, an oral orexin receptor 2 (OX2R) agonist, on cognitive symptoms in 112 adults with narcolepsy type 1 (NT1). Participants were randomised to various doses of oveporexton or placebo over eight weeks.
The study found that oveporexton significantly improved attention, memory, and executive function with higher doses carrying generally larger effect sizes. These findings suggest that OX2R stimulation can effectively address the cognitive burdens of NT1 beyond just managing sleepiness and cataplexy.
Early Tofersen Initiation Slows Disease Progression in SOD1-ALS
This analysis of the phase 3 VALOR study and its open-label extension (OLE) evaluated the long-term efficacy and safety of tofersen, an antisense oligonucleotide designed to reduce SOD1 protein synthesis. The study followed 108 participants with SOD1-associated amyotrophic lateral sclerosis (ALS) for up to 3.5 years, comparing those who started treatment early to those in a placebo/delayed-start group who began therapy approximately six months later.
The early-start group showed a smaller decrease in the ALS Functional Rating Scale–Revised score (−9.9 vs −13.5 points) and respiratory function (slow vital capacity, −13.8% vs −18.1%) compared to the delayed-start group. Adverse events were consistent with ALS progression or the lumbar puncture, and all serious neurological events were reversible. These final data provide a clear rationale for the early initiation of tofersen to preserve function and extend survival in patients with SOD1-ALS.
Read the paper here: Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis | Amyotrophic Lateral Sclerosis | JAMA Neurology | JAMA Network
AI-Driven Emulated Trials Reveal Comparative Effectiveness of Anti-Seizure Medications
This retrospective cohort study utilised a causal inference and informatics-based framework to emulate clinical trials, leveraging natural language processing to extract data from electronic health records of nearly 3,000 patients. The trial aimed to provide comparative effectiveness data for first, second, and third-line therapies across different epilepsy types.
For first-line treatment across all epilepsy types, levetiracetam and lamotrigine were superior to oxcarbazepine in achieving seizure freedom over two years, while levetiracetam demonstrated the highest drug retention rate over five years. In focal epilepsy, first-line drugs achieved similar seizure freedom, yet levetiracetam showed the highest retention rates.
These findings highlight that emulated clinical trials using real-world data can identify significant differences in ASM performance, provide a valuable evidence base for personalising epilepsy treatment, and generate hypotheses for future prospective trials.
Read the paper here: Comparative effectiveness of anti-seizure medications in emulated trials using medical informatics | Brain | Oxford Academic
