New and emerging pharmacotherapy for duchenne muscular dystrophy: a focus on synthetic therapeutics

Introduction: Duchenne muscular dystrophy (DMD) is the result of X-chromosome-linked mutations to the dystrophin protein gene that prevent the normal development and repair of muscles leading to muscle deterioration. The condition affects nearly 1 in 3,500 males worldwide. Current therapeutics have not been sufficient in providing a cure or resulting in a significant extension in life expectancy, but many therapeutic options are currently under investigation. Areas covered: This article provides an overview of the current and emerging therapies for DMD giving particular focus to synthetic therapeutic options. The authors further provide their expert opinion. Expert opinion: Many discrepancies in primary outcomes of trials have led to questions of efficacy for medications, as well as difficulty in securing FDA approval. A standardization of primary outcome strategies, as well as better access to investigational medications, may alleviate some of the controversy and pressures that exist on medication approvals. Many trials have identified cohorts who responded more favorably to medications, despite a lack of significance in the overall intent-to-treat populations. This indicates that more medication screening and personalized treatment with patient-specific targeting might deliver more clinically significant results

Translational obstacles with off-label drug use in acute traumatic brain injury

Traumatic brain injury results in significant morbidity and mortality, and there is an urgent need for neuroprotective medications that can prevent the persisting symptoms and disabilities following injury. Several existing pharmacotherapies have been targeted for off-label benefit in traumatic brain injury, as these agents are well characterized and commercially available, easing the process of clinical trial development. Despite promising results in animal models, clinical trials have demonstrated minimal benefit. One possible reason for these failed translations could be that drug selection, characterization and dosing are not routinely established in the appropriate early phase trials before larger scale testing. Examining how recent trials may have bypassed these steps may help future trials to more definitively determine the efficacy of potential therapeutics

The prevalence of disability in the oldest-old is high and continues to increase with age: findings from The 90+ Study.

ObjectivesTo examine the prevalence and type of disability in the oldest-old (90+), the fastest growing age group in the United States.MethodsThe current study included functional data on 697 participants from The 90+ Study, a population-based longitudinal study of aging and dementia in people aged 90 and older. Data were obtained by participant's informants via a written questionnaire. The prevalence of disability was calculated for two definitions using activities of daily living (ADLs). ADL difficulty was defined as difficulty with one or more ADLs whereas ADL dependency was defined as needing help on one or more ADLs.ResultsADL difficulty was present in 71% in 90-94 year olds, 89% in 95-99 year olds, and 97% in centenarians. ADL dependency was present in 44% of 90-94 year olds, 66% of 95-99 year olds, and 92% of centenarians. The ADL most commonly causing difficulty was walking (70%) whereas the ADL most commonly causing dependency was bathing (51%). Age, gender, and institutionalization were significantly associated with both ADL difficulty and ADL dependency.ConclusionsSimilar to studies in younger individuals, the current study suggests that the prevalence of disability continues to increase rapidly in people aged 90 and older. With the rapid growth in the number of people in this age group, disability in the oldest-old has major public health implications

Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease that primarily affects young males. Patients with DMD are unable to produce dystrophin, a crucial protein found in myocytes, leading to a loss of muscle support and integrity. Corticosteroids are the standard supportive treatment for DMD; however, there is a high demand to expand the number of safe, effective pharmacologic options. Recently a surge of new therapeutics for DMD is offering hope to patients. A variety of these new medications, such as stop codon readthrough agents, exon-skipping agents, and utrophin modulators, aim to replace dystrophin in myocytes. Other new therapeutics aim to prevent or repair muscle damage caused by the absence of dystrophin. This review provides an update on the medications being investigated in DMD