Science translational medicine
-
The Patient Protection and Affordable Care Act created the Patient-Centered Outcomes Research Institute (PCORI), a nonprofit corporation that is neither an agency nor an establishment of the U. S. government. PCORI's mission is to support the production of well-validated scientific evidence to assist the nation in making informed decisions about a broad range of health care-related issues. In this Commentary, the directors of the Agency for Healthcare Research and Quality and the National Institutes of Health discuss PCORI's opportunities to contribute to a robust portfolio of scientific inquiry that builds on their agencies' investment in comparative effectiveness research.
-
Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes. ⋯ Moreover, after introduction of bacteria into their lungs, pigs with CF failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Our finding that pigs with CF have a host defense defect against bacteria within hours of birth provides an opportunity to further investigate CF pathogenesis and to test therapeutic and preventive strategies that could be deployed before secondary consequences develop.
-
Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SUR1), in progressive hemorrhagic necrosis. ⋯ The beneficial effects of Abcc8 suppression were associated with prevention of oncotic (necrotic) death of capillary endothelial cells. Suppression of Abcc8 with antisense oligodeoxynucleotide after SCI presents an opportunity for reducing the devastating sequelae of SCI.
-
Worldwide, traumatic brain injury (TBI) is a major cause of mortality and morbidity with a substantial predicted increase in incidence. Despite an obvious need, there are no pharmacological treatment options for TBI because translation of neuroprotection from preclinical studies to clinical practice has so far failed. ⋯ We suggest that the monitoring and investigation tools that are commonly used in patients with TBI may provide an experimental medicine route to facilitate a more rational approach to translational research. This suggestion is underpinned by existing research data on disease biology, drug delivery, and treatment response obtained with these methods.
-
The Commentary of Mills and Sykes in Science Translational Medicine presented their thesis on the advent of high-throughput technologies and the dangers they may represent for the future of biomedical research. In response, we argue that true progress on the diagnosis and treatment of common human diseases will require the advent of big biology and its deep integration with focused research as practiced in both academic and industrial institutions.