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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The next phase of clinical trials in neonatal encephalopathy (NE) focuses on hypothermia adjuvant therapies targeting alternative recovery mechanisms during the process of hypoxic brain injury. Identifying infants eligible for neuroprotective therapies begins with the clinical detection of brain injury and classification of severity. Combining a variety of biomarkers (serum, clinical exam, EEG, movement patterns) with innovative clinical trial design and analyses will help target infants with the most appropriate and timely treatments. The timing of magnetic resonance imaging (MRI) and MR spectroscopy after NE both assists in identifying the acute perinatal nature of the injury (days 3-7) and evaluates the full extent and evolution of the injury (days 10-21). Early, intermediate outcome of neuroprotective interventions may be best defined by the 21-day neuroimaging, with recognition that the full neurodevelopmental trajectory is not yet defined. An initial evaluation of each new therapy at this time point may allow higher-throughput selection of promising therapies for more extensive investigation. Functional recovery can be assessed using a trajectory of neurodevelopmental evaluations targeted to a prespecified and mechanistically derived hypothesis of drug action. As precision medicine revolutionizes healthcare, it should also include the redesign of NE clinical trials to allow safe, efficient, and targeted therapeutics. IMPACT: As precision medicine revolutionizes healthcare, it should also include the redesign of NE clinical trials to allow faster development of safe, effective, and targeted therapeutics. This article provides a multidisciplinary perspective on the future of clinical trials in NE; novel trial design; study management and oversight; biostatistical methods; and a combination of serum, imaging, and neurodevelopmental biomarkers can advance the field and improve outcomes for infants affected by NE. Innovative clinical trial designs, new intermediate trial end points, and a trajectory of neurodevelopmental evaluations targeted to a prespecified and mechanistically derived hypothesis of drug action can help address common challenges in NE clinical trials and allow for faster selection and validation of promising therapies for more extensive investigation.
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PMID:Perspectives from the Society for Pediatric Research. Neonatal encephalopathy clinical trials: developing the future. 3222 74

Numerous studies have examined the potential use of therapeutic gases for the treatment of various neurological disorders. Hydrogen gas, a promising neuroprotective agent, has been a focus of study due to its potent antioxidative properties. In translational research into adult diseases, hydrogen has been shown to be neuroprotective in disorders such as cerebral ischemia and traumatic brain injury, and in neurodegenerative diseases such as Alzheimer's disease. Animal and human studies have verified the safety and feasibility of molecular hydrogen. However, despite extensive research on its efficacy in adults, only a few studies have investigated its application in pediatric and neonatal medicine. Neonatal hypoxic-ischemic encephalopathy (HIE) is characterized by damage to neurons and other cells of the nervous system. One of the major contributing factors is excessive exposure to oxidative stress. Current research interest in HIE is shifting toward new neuroprotective agents, as single agents or as adjuncts to therapeutic hypothermia. Here, we review therapeutic gases, particularly hydrogen, and their potentials and limitations in the treatment of HIE in newborns. IMPACT: Translational animal models of neonatal HIE are a current focus of research into the therapeutic usefulness of various gases. Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models. The optimal target severity for therapeutic interventions should be well established to improve outcomes.
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PMID:Hydrogen and therapeutic gases for neonatal hypoxic-ischemic encephalopathy: potential neuroprotective adjuncts in translational research. 3250 23