Assuntos
Compostos Organofosforados/uso terapêutico , Pterinas/uso terapêutico , Animais , Estudos Clínicos como Assunto , Humanos , Estimativa de Kaplan-Meier , Erros Inatos do Metabolismo dos Metais/mortalidade , Molibdoferredoxina/efeitos dos fármacos , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/farmacologia , Pterinas/efeitos adversos , Pterinas/farmacologia , Estados Unidos , United States Food and Drug AdministrationRESUMO
Fosdenopterin (NulibryTM) is a synthetic cyclic pyranopterin monophosphate that is being developed by Origin Biosciences (a subsidiary of BridgeBio Pharma) for the treatment of molybdenum cofactor deficiency (MoCD) type A. Fosdenopterin was recently approved by the US FDA for use in reducing the risk of mortality in paediatric and adult patients with MoCD type A. This article summarizes the milestones in the development of fosdenopterin leading to this first approval.
Assuntos
Erros Inatos do Metabolismo dos Metais/tratamento farmacológico , Compostos Organofosforados/uso terapêutico , Pterinas/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Humanos , Erros Inatos do Metabolismo dos Metais/mortalidade , Erros Inatos do Metabolismo dos Metais/fisiopatologia , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/farmacologia , Pterinas/efeitos adversos , Pterinas/farmacologiaRESUMO
Neonatal encephalopathy with seizures is a presentation in which rapid whole-genome sequencing (rWGS) has shown clinical utility and improved outcomes. We report a neonate who presented on the third day of life with seizures refractory to antiepileptic medications and neurologic and computerized tomographic findings consistent with severe generalized brain swelling. rWGS revealed compound heterozygous variants in the molybdenum cofactor synthesis gene, type 1A (MOCS1 c.*7 + 5G > A and c.377G > A); a provisional diagnosis of molybdenum cofactor deficiency on day of life 4. An emergency investigational new drug application for intravenous replacement of the MOCS1 product, cyclic pyranopterin monophosphate, was considered, but felt unsuitable in light of the severity of disease and delay in the start of treatment. The patient died on day of life 9 despite having a precise molecular diagnosis within the first week of life. This case illustrates that an rWGS-based molecular diagnosis within the first week of life may be insufficient to improve outcomes. However, it did inform clinical decision-making with regard to resuscitation and predicted long-term outcome. We suggest that to achieve optimal reductions in morbidity and mortality, rWGS must be implemented within a comprehensive rapid precision medicine system (CRPM). Akin to newborn screening (NBS), CRPM will have onboarding, diagnosis, and precision medicine implementation components developed in response to patient and parental needs. Education of health-care providers in a learning model in which ongoing data analyses informs system improvement will be essential for optimal effectiveness of CRPM.
