(Press-News.org) (SACRAMENTO, Calif.) -- In its first clinical application in pediatric patients, an investigational medication developed and manufactured at UC Davis has been found to effectively treat children with life-threatening and difficult-to-control epileptic seizures without side effects, according to a research report by scientists at UC Davis and Northwestern University.
The investigational formulation of allopregnanolone was manufactured by UC Davis Health System's Good Manufacturing Practice Laboratory. Two children were treated with the allopregnanolone formulation, one at UC Davis Children's Hospital, the other at the Ann & Robert Lurie Children's Hospital in Chicago. Both children were weaned from general anesthetics and other seizure treatments and their seizures resolved. In both instances the children are recovering.
The research is published online in Annals of Neurology, an official journal of the American Neurological Association and the Child Neurology Society.
Super-refractory status epilepticus is a condition diagnosed in patients with refractory status epilepticus being treated with infusions of general anesthetics when seizures continue for longer than 24 hours, despite anesthesia, or when seizures recur on reduction or withdrawal of the anesthesia. Super-refractory status epilepticus has high morbidity and mortality. There are no Food and Drug Administration (FDA)-approved treatments for the condition.
Allopregnanolone is a positive allosteric modulator of GABAA receptors in the brain. Research in animals has shown that allopregnanolone protects against seizures and can stop status epilepticus. Although the allopregnanolone used to manufacture the investigational treatment was produced by chemical synthesis according to procedures regulated by the FDA, it is synthesized normally in small quantities in the body from progesterone.
"Our laboratory studies have shown that allopregnanolone is effective in stopping status epilepticus that is refractory to treatment," said Michael Rogawski, professor in the UC Davis Department of Neurology and a co-author of the report.
In both of the clinical cases, the patients continued to have seizures despite weeks of intensive treatment with medications, including infusion of anesthetics. Emergency treatment with the investigational medication was approved by the FDA; the two patients received the medication over a five-day period, during which time both were weaned from anesthetics and other seizure medications. Status epilepticus did not recur after treatment. There were no adverse drug effects, the researchers said.
Mortality rates in super-refractory status epilepticus can be as high as 50 percent, and those who survive experience high rates of subsequent neurological impairment. The authors note that progesterone and ganaxolone, a chemical analog of allopregnanolone, have been studied in clinical trials for epilepsy and have shown benefit. Researchers at UC Davis, led by Rogawski, currently are investigating the use of allopregnanolone as a treatment for traumatic brain injury.
"Neurosteroids, including allopregnanolone, are a promising treatment for epilepsy and refractory status epilepticus that may overcome resistance to benzodiazepines and barbiturates and facilitate the withdrawal of these agents by preventing rebound seizures, a key problem in treatment of super-refractory status epilepticus," Rogawski said.
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Other authors include JoAnne Natale and Celia Chang of UC Davis; Mark S. Wainwright, Eileen Broomall, Michele Grimason, Joshua Goldstein and Craig M. Smith of Ann & Robert Lurie Children's Hospital and Northwestern University; and Stephen Kanes of Sage Therapeutics. Rogawski serves as a consultant to Sage, which has rights to commercialize the treatment.
UC Davis Health System improves health and health care, around the corner and across the globe. Diverse in expertise but united in purpose, UC Davis faculty, staff and students collaborate daily to solve urgent real-world problems, translate research into new cures and eliminate health disparities. Whether treating complex injuries, improving cancer care or explaining autism, UC Davis Health System's unique combination of academic excellence and social responsibility advances health for all. For more information, visit http://healthsystem.ucdavis.edu.
LA JOLLA, CA - November 12, 2014 - Driving to work becomes routine--but could you drive the entire way in reverse gear? Humans, like many animals, are accustomed to seeing objects pass behind us as we go forward. Moving backwards feels unnatural.
In a new study, scientists from The Scripps Research Institute (TSRI) reveal that moving forward actually trains the brain to perceive the world normally. The findings also show that the relationship between neurons in the eye and the brain is more complicated than previously thought--in fact, the order in which we see things ...
(MEMPHIS, Tenn. - November 12, 2014) An international collaboration has identified frequent mutations in two genes that often occur together in Ewing sarcoma (EWS) and that define a subtype of the cancer associated with reduced survival. The research, conducted by the St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project and the Institut Curie-Inserm through the International Cancer Genome Consortium, appears in the current issue of the scientific journal Cancer Discovery.
Mutations in the genes STAG2 and TP53 have previously been ...
Giant otters may have a vocal repertoire with 22 distinct vocalization types produced by adults and 11 neonate vocalization types, according to a study published November 12, 2014 in the open-access journal PLOS ONE by Christina Mumm and Mirjam Knörnschild from University of Ulm, Germany.
Giant otters, found in South America, are very social and frequently vocalizing animals. They live in groups that may vary, but generally include a reproductive pair and their offspring, born in different years. Individuals engage in shared group activities and hold different social ...
Using fewer than twenty genomes, researchers were unable to find rare protein-altering variants significantly associated with extreme longevity, according to a study published November 12, 2014 in the open-access journal PLOS ONE by Hinco Gierman from Stanford University and colleagues.
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An educational approach in kindergarten focused on the development of executive functions--the ability to avoid distractions, focus attention, hold relevant details in working memory, and regulate impulsive behavior--in children improved academic learning in and beyond kindergarten, helping to overcome deficits in school readiness associated with poverty, according to a study published November 12, 2014 in the open-access journal PLOS ONE by Clancy Blair and C. Cybele Raver from New York University.
Based on the results, the authors suggest that executive function ...
An educational approach focused on the development of children's executive functions - the ability to avoid distractions, focus attention, hold relevant information in working memory, and regulate impulsive behavior - improved academic learning in and beyond kindergarten, according to a new study by researchers at NYU's Steinhardt School of Culture, Education, and Human Development.
Because some effects were especially pronounced in high-poverty schools, the findings hold promise for closing the poverty-related achievement gap and suggest that an emphasis on executive ...
The normally bland face of Uranus has become increasingly stormy, with enormous cloud systems so bright that for the first time ever, amateur astronomers are able to see details in the planet's hazy blue-green atmosphere.
"The weather on Uranus is incredibly active," said Imke de Pater, professor and chair of astronomy at the University of California, Berkeley, and leader of the team that first noticed the activity when observing the planet with adaptive optics on the W. M. Keck II Telescope in Hawaii.
"This type of activity would have been expected in 2007, when Uranus's ...
In the fight against HIV, microbicides--chemical compounds that can be applied topically to the female genital tract to protect against sexually transmitted infections--have been touted as an effective alternative to condoms. However, while these compounds are successful at preventing transmission of the virus in a petri dish, clinical trials using microbicides have largely failed. A new study from the Gladstone Institutes and the University of Ulm now reveals that this discrepancy may be due to the primary mode of transportation of the virus during sexual transmission, ...
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The video illustrates the complete experiment. First the participant shown wearing the Oculus head-mounted display and the OptiTrack motion capture suit gives comfort to the crying virtual child. We see...
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Self-compassion can be learned using avatars in an immersive virtual reality, finds new research led by UCL. This innovative approach reduced self-criticism and increased self-compassion and feelings of contentment in naturally self-critical ...
It is claimed one in five students have taken the 'smart' drug Modafinil to boost their ability to study and improve their chances of exam success. But new research into the effects of Modafinil has shown that healthy students could find their performance impaired by the drug.
The study carried out by Dr Ahmed Dahir Mohamed, in the School of Psychology at The University of Nottingham Malaysia Campus, and published today, Wednesday 12 November 2014, in the open access journal PLOS ONE, showed the drug had negative effects in healthy people.
Dr Mohamed said: "We looked ...
