by Isabella Colonna and 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 July 2026.
For our Research Paper of the Month, go here: Research Paper of the Month: Consensus Meta-Analysis of Genome-Wide Association Studies for Alzheimer’s Disease and Related Dementias – eanNews
Acetazolamide in Idiopathic Normal Pressure Hydrocephalus: A Negative Phase 2 Trial
Idiopathic normal pressure hydrocephalus (iNPH) affects approximately 1–2% of individuals aged 70 years and older and is associated with progressive functional decline. Currently, ventriculoperitoneal shunt surgery represents the only established treatment for this condition, although it carries a relatively high risk of complications. This randomised, double-blind, placebo-controlled phase 2 trial, conducted in Sweden, investigated the safety, tolerability, and efficacy of acetazolamide as a potential pharmacological treatment for patients with iNPH. A total of 50 participants were randomly assigned to receive either acetazolamide (n = 25) or placebo (n = 25). Acetazolamide was administered orally, with individualised dose titration up to 250mg twice daily. Treatment was continued until the patient underwent shunt surgery or for a maximum duration of nine months. At the end-of-treatment assessment (median treatment duration: 121 days in the acetazolamide group and 187 days in the placebo group), acetazolamide did not result in any significant improvement in gait compared with placebo. Adverse events were more frequent among patients receiving acetazolamide, although no serious adverse events were considered related to the study medication. Overall, the findings indicate that acetazolamide neither improved gait performance nor demonstrated acceptable tolerability in patients with idiopathic normal pressure hydrocephalus. These results do not support the use of acetazolamide as an effective pharmacological treatment for this condition.
Brepocitinib in Treatment-Refractory Dermatomyositis: Results from the Phase 3 VALOR Trial
Dermatomyositis is a systemic autoimmune disease characterised by chronic inflammation and progressive damage affecting multiple organs, including skeletal muscles, skin, lungs, joints, heart, and gastrointestinal tract. The VALOR study was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted over 52 weeks to evaluate the efficacy and safety of brepocitinib, an oral selective inhibitor of tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1), in adults with dermatomyositis. Participants were randomly assigned to receive oral brepocitinib 30mg once daily (n=81), brepocitinib 15mg once daily (n=81), or placebo (n=79). All participants had experienced an inadequate response to at least one conventional therapy before enrollment. At week 52, brepocitinib 30mg demonstrated significant improvements compared with placebo across several clinically relevant outcomes, with treatment effects becoming apparent as early as week four. Serious infections occurred more frequently in the 30mg brepocitinib group than in the placebo group; however, no deaths were reported during the study. Overall, these findings suggest that brepocitinib 30mg may represent an effective therapeutic option for patients with treatment-refractory dermatomyositis, although its use should be balanced against the increased risk of serious infections.
Read the paper here: A Phase 3 Trial of Brepocitinib in Dermatomyositis | New England Journal of Medicine
Oral Semaglutide Fails to Slow Clinical Progression in Early Alzheimer’s Disease
Increasing evidence from animal, clinical, and real-world studies in individuals with type 2 diabetes and obesity has previously suggested that exposure to glucagon-like peptide-1 (GLP-1) receptor agonists could reduce the risk of dementia and Alzheimer’s disease through potential neuroprotective mechanisms. To evaluate this causal effect, the multicentre, randomised, double-blind, placebo-controlled phase 3 evoke and evoke+ trials investigated the efficacy and safety of oral semaglutide (up to 14 mg once daily) over 156 weeks in 3,808 participants aged 55–85 years with amyloid-confirmed early Alzheimer’s disease (mild cognitive impairment or mild dementia). A total of 1,855 participants were randomised in evoke (semaglutide, n=928; placebo, n=927) and 1,953 in evoke+ (semaglutide, n=976; placebo, n=977), the latter specifically enrolling individuals with significant small vessel pathology (n=54, 2.8%).
Both trials were prematurely discontinued due to negative clinical outcomes. The primary endpoint, defined as the change in the Clinical Dementia Rating—Sum of Boxes (CDR-SB) score from baseline to week 104, demonstrated no significant differences between the treatment and control arms. In the evoke trial, the mean change in CDR-SB score was 2.3 (SE 0.1) for both the semaglutide and placebo groups, resulting in an estimated difference of −0.08 (95% CI −0.35 to 0.20; p=0.57). In the evoke+ trial, the mean change was 2.2 (0.1) with semaglutide compared to 2.1 (0.1) with placebo, yielding an estimated difference of 0.10 (95% CI −0.17 to 0.38; p=0.46). Safety assessments showed treatment-emergent adverse events in 91.2% (1,729/1,896) of participants receiving semaglutide versus 84.8% (1,613/1,902) receiving placebo. These findings indicate that oral semaglutide is not efficacious in slowing clinical decline in early Alzheimer’s disease, establishing a safety profile consistent with studies in other therapeutic indications.
