Evolving Role of Viltolarsen for Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data.

Children's motor imagery modality dominance modulates the role of attentional focus in motor skill learning.

We investigated whether children's motor imagery dominance modulated the relationship between attentional focus and motor learning of a tossing task. One hundred and thirty-eight boys (age: M = 10.13, SD = 0.65) completed the Movement Imagery Questionnaire - Children (MIQ-C) to determine imagery modality dominance (kinesthetic, internal-visual, external-visual) and were randomly assigned to either an internal (n = 71) or external (n = 67) attentional focus group. Participants completed 60 trials of a tossing task with their non-dominant hand on day 1. Participants in the internal focus group were asked "to focus on the throwing arm", whereas participants in the external focus group were instructed "to focus on the ball." A retention test was conducted 24 h later to assess motor learning. Overall, the results from a nested, multiple linear regression analysis indicated the degree to which internal or external focus influences children's throwing accuracy is dependent upon their motor imagery modality dominance. Specifically, higher levels of external-visual imagery dominance resulted in greater motor learning for children adopting an external focus. In contrast, higher values of kinesthetic imagery dominance resulted in reduced motor learning for children who adopted an external focus. Despite the need for future research, we recommend motor imagery modality dominance assessments be considered when investigating the influence of attentional focus on motor learning, particularly when the target population is children.