Viltolarsen: a treatment option for Duchenne muscular dystrophy patients who are amenable to exon 53 skipping therapy.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a progressive genetic disease leading to muscular weakness. DMD is caused by mutations of the dystrophin gene on the X chromosome that is responsible for production of dystrophin protein. Dystrophin contributes to structural support in muscle cells and mutations result in dystrophin protein deficiency which causes muscle damage and the associated clinical presentation. Exon skipping medications, including the exon 53 targeting viltolarsen, are the first agents with the ability to partially restore dystrophin protein. AREAS COVERED: Herein, the authors profile viltolarsen for the DMD patients who are amenable to exon 53 skipping therapy and provide their expert perspectives on this subject. EXPERT OPINION: Current findings suggest that viltolarsen could play a role in the current and possible future treatment of DMD. Viltolarsen seems to be safe and restores dystrophin protein to around 6% of the normal level. Due to orphan drug status, after the completion of the phase 2 clinical trial, viltolarsen was granted accelerated approval in Japan and in the US. A phase 3 trial is currently in progress and needs to earn full approval. Although a multidisciplinary approach continues to be critical, the addition of exon skipping agents like viltolarsen may improve the quality of patients' lives. However, data on the long-term safety and efficacy of this medication are not yet available due to its recent accelerated approval.

Automated quantification of atrophy and acute ischemic volume for outcome prediction in endovascular thrombectomy.

Background: Short- and long-term outcomes from endovascular thrombectomy (EVT) for large vessel occlusion stroke remain variable. Numerous relevant predictors have been identified, including severity of neurological deficits, age, and imaging features. The latter is typically defined as acute changes (most commonly Alberta Stroke Programme Early CT Score, ASPECTS, at presentation), but there is little information on the impact of imaging assessment of premorbid brain health as a determinant of outcome. Aims: To examine the impact of automated measures of stroke severity and underlying brain frailty on short- and long-term outcomes in acute stroke treated with EVT. Methods: In 215 patients with anterior circulation stroke, who subsequently underwent EVT, automated analysis of presenting non-contrast CT scans was used to determine acute ischemic volume (AIV) and e-ASPECTS as markers of stroke severity, and cerebral atrophy as a marker of brain frailty. Univariate and multivariate logistic regression were used to identify significant predictors of NIHSS improvement, modified Rankin scale (mRS) at 90 and 30 days, mortality at 90 days and symptomatic intracranial hemorrhage (sICH) following successful EVT. Results: For long-term outcome, atrophy and presenting NIHSS were significant predictors of mRS 0-2 and death at 90 days, whereas age did not reach significance in multivariate analysis. Conversely, for short-term NIHSS improvement, AIV and age were significant predictors, unlike presenting NIHSS. The interaction between age and NIHSS was similar to the interaction of AIV and atrophy for mRS 0-2 at 90 days. Conclusion: Combinations of automated software-based imaging analysis and clinical data can be useful for predicting short-term neurological outcome and may improve long-term prognostication in EVT. These results provide a basis for future development of predictive tools built into decision-aiding software in stroke.