Precision medicine for genetic childhood movement disorders.

Increasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient-centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or disease mechanism. In tandem with these scientific advances, close collaboration between clinicians, researchers, affected families, and stakeholders in the wider community will be key to successfully delivering such precision therapies to children with movement disorders. What this paper adds Precision medicine for genetic childhood movement disorders is developing rapidly. Accurate diagnosis, disease-specific outcome measures, and collaborative multidisciplinary work will accelerate the progress of such strategies.

The role of manganese dysregulation in neurological disease: emerging evidence.

Manganese is an essential trace metal. The dysregulation of manganese seen in a broad spectrum of neurological disorders reflects its importance in brain development and key neurophysiological processes. Historically, the observation of acquired manganism in miners and people who misuse drugs provided early evidence of brain toxicity related to manganese exposure. The identification of inherited manganese transportopathies, which cause neurodevelopmental and neurodegenerative syndromes, further corroborates the neurotoxic potential of this element. Moreover, manganese dyshomoeostasis is also implicated in Parkinson's disease and other neurodegenerative conditions, such as Alzheimer's disease and Huntington's disease. Ongoing and future research will facilitate the development of better targeted therapeutical strategies than are currently available for manganese-associated neurological disorders.

Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation.

Background: Neurodegeneration with brain iron accumulation (NBIA) disorders comprise a group of rare but devastating inherited neurological diseases with unifying features of progressive cognitive and motor decline, and increased iron deposition in the basal ganglia. Although at present there are no proven disease-modifying treatments, the severe nature of these monogenic disorders lends to consideration of personalized medicine strategies, including targeted gene therapy. In this review we summarize the progress and future direction towards precision therapies for NBIA disorders. Methods: This review considered all relevant publications up to April 2021 using a systematic search strategy of PubMed and clinical trials databases. Results: We review what is currently known about the underlying pathophysiology of NBIA disorders, common NBIA disease pathways, and how this knowledge has influenced current management strategies and clinical trial design. The safety profile, efficacy and clinical outcome of clinical studies are reviewed. Furthermore, the potential for future therapeutic approaches is also discussed. Discussion: Therapeutic options in NBIAs remain very limited, with no proven disease-modifying treatments at present. However, a number of different approaches are currently under development with increasing focus on targeted precision therapies. Recent advances in the field give hope that novel strategies, such as gene therapy, gene editing and substrate replacement therapies are both scientifically and financially feasible for these conditions. Highlights: This article provides an up-to-date review of the current literature about Neurodegeneration with Brain Iron Accumulation (NBIA), with a focus on disease pathophysiology, current and previously trialed therapies, and future treatments in development, including consideration of potential genetic therapy approaches.

Pulmonary hemorrhage as a complication of Respiratory Syncyntial Virus (RSV) bronchiolitis.

Respiratory Syncytial Virus (RSV) is a common cause of bronchiolitis. Although there are a number of recognized complications, pulmonary hemorrhage has not been reported previously. A retrospective case notes review was performed through an electronic search of a Pediatric Intensive Care Unit's medical records. Seven patients with RSV infection and pulmonary hemorrhage were identified and included in this case series. Six of the seven patients were born prematurely (30-36 weeks gestation). All patients required blood transfusion. The pulmonary hemorrhage events all occurred after a period of mechanical ventilation and following extubation. All of the patients required reintubation with a mean of 5 further days of mechanical ventilation. Pulmonary hemorrhage is an uncommon complication of RSV infection, which has not been reported previously in the literature. Further studies are required to determine incidence, pathogenesis, and outcome. Pediatr Pulmonol. 2017;52:E32-E36. © 2016 Wiley Periodicals, Inc.