Seizures, Febrile

Pictured: A hand pointing to an upward stock chart on a screen/iStock, tadamichi Stoke Therapeutics on Monday reported positive Phase I/IIa data for its Dravet syndrome candidate and now hopes to leapfrog straight into a registrational study. The news sent the company’s stock skyrocketing 98% in Tuesday morning trading. Patients receiving a 70-mg dose of STK-001 achieved median reductions of 85% in convulsive seizure frequency at three months, on top of their current regimen of anti-seizure medicines. An open label extension study showed continued dosing of 30 mg and 45 mg, respectively, achieved durable seizure reduction and “clinically meaningful” improvements in cognition and behavior over 12 months. Stoke reported the improvements are in “stark contrast” to a natural history study that showed most patients not only had no meaningful reduction of seizures, but also had widening gaps in cognition and behavior despite treatment with anti-seizure medications. The FDA has now cleared patients to receive three doses at 70 mg followed by continued dosing at 45 mg. Stoke announced plans to meet with the agency regarding a registrational study of that treatment plan. Dravet syndrome is a rare, severe genetic epilepsy that begins in the first treatment of life. It’s characterized by prolonged, repeated and sometimes febrile seizures that are treatment resistant. It carries a higher mortality rate than other epileptic conditions, with up to 20% of children never reaching adulthood. Most children with the syndrome also suffer from intellectual disability and development delays among other comorbidities. There is no cure and current anti-seizure medicines often do not offer the seizure control needed. Stoke’s candidate has the potential to be the first disease-modifying therapy targeting the genetic cause of Dravet syndrome. Administered by spinal tap, the antisense oligonucleotide leverages the non-mutated copy of the patient’s gene to restore function of the lacking sodium channel protein. This is a vastly different approach than current anti-seizure medications which work by reducing abnormal electrical activity in the brain. Encoded Therapeutics received IND clearance from the FDA in February 2024 for its Dravet syndrome gene therapy candidate. The treatment aims to be a one-time gene regulation therapy targeting the SCN1A gene. The two-part, Phase I/II trial will begin in the first half of this year. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

Viral infections trigger more cases of intussusception, the common cause of bowel blockages in young children, than previously thought, according to a new study. Viral infections trigger more cases of intussusception, the common cause of bowel blockages in young children, than previously thought, according to a new study. The research, led by Murdoch Children's Research Institute (MCRI) and published in Clinical Infectious Diseases, found during the COVID-19 lockdowns hospital admissions for intussusception, a medical emergency involving obstruction of the intestine, among young children significantly decreased. For the study, 12 years of data was analysed across Victoria, NSW and Queensland. A total of 5,589 intussusception cases were recorded between January, 2010 and April, 2022. Of those, 3,179 were children under the age of two. During the lockdown periods, Victoria and NSW experienced a decline in hospital admissions for intussusception among children under two by 62.7 per cent and 40.1 per cent, respectively. The rate of intussusception cases has now returned to normal levels. MCRI and Monash University researcher Dr Ben Townley said the magnitude of the decline supported that common respiratory diseases such as colds, the flu and respiratory syncytial virus (RSV), were behind a significant proportion of intussusception cases. "Reductions in intussusception hospital admissions were seen in all age groups, however most occurred in children less than two years of age," he said. "Intussusception is the leading cause of acute bowel obstruction in infants and young children and without prompt diagnosis and management, can be fatal. "Countries with prolonged COVID-19 lockdowns and suppression strategies saw reductions in common respiratory viruses, which influenced the drop in intussusception admissions." Victoria experienced the greatest lockdown duration, with Melbourne having six lockdown periods, for a total of 263 days. Greater Sydney had 159 days and Brisbane had 18 days in lockdown. MCRI Professor Jim Buttery said the decrease in intussusception cases was greater than expected given previous research into the causes of the condition. "Our analysis found commons viruses play a larger role than previously recognised in triggering intussusception," he said. Infectious triggers were thought to comprise only a minority, about 30 per cent, of cases." Professor Buttery said the findings raised the possibility that emerging vaccines like the new RSV vaccines may help prevent intussusception. "When a new vaccine against common childhood respiratory viruses is introduced, we may find there are some unexpected benefits, like protecting more children from intussusception," he said. We last saw this in 2007, when introducing the rotavirus vaccine against gastroenteritis, also reduced febrile convulsions in young children." Researchers fromSydney Children's Hospital Network, University of Melbourne and Queensland Health also contributed to the findings.

NEW YORK, Jan. 4, 2024 /PRNewswire/ -- In a study designed to better understand sudden, unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures, accompanied by muscle convulsions, as a potential cause. Experts estimate in excess of 3,000 families each year in the United States lose a baby or young child unexpectedly and without explanation. Most are infants in what is referred to as sudden infant death syndrome, or SIDS, but 400 or more cases involve children aged 1 and older, and in what is called sudden unexplained death in children (SUDC). Over half of these children are toddlers. The study findings come from a registry of more than 300 SUDC cases, set up a decade ago by researchers at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers between the ages of 1 and 3 that were potentially attributable to seizures. These seizures lasted less than 60 seconds and occurred within 30 minutes immediately prior to each child's death, say the study authors. For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health. Publishing in the journal Neurology online Jan. 4, the new study involved an analysis by a team of eight physicians of the rare SUDC cases for which there were also home video recordings, from either security systems or commercial crib cameras, made while each child was sleeping on the night or afternoon of their death. Five of seven recordings were running nonstop at the time and showed direct sound and visible motion indicative of a seizure happening. The remaining two recordings were triggered by sound or motion, but only one suggested that a muscle convulsion, a sign of seizure, had occurred. As well, only one toddler had a documented previous history of febrile seizures. All children in the study had previously undergone an autopsy that revealed no definitive cause of death. "Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep," said study lead investigator Laura Gould, M.Sc., MA, PT, a research assistant professor at NYU Langone. Gould lost her daughter, Maria, to SUDC at the age of 15 months in 1997, a tragedy that prompted her successful lobby for establishment of the NYU SUDC Registry and Research Collaborative. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure. "These study findings show that seizures are much more common than patients' medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults," said study senior investigator and neurologist Orrin Devinsky, MD. Devinsky, a professor in the Departments of Neurology, Neurosurgery, and Psychiatry at NYU Langone, as well as chief of its epilepsy service, adds that "convulsive seizures may be the 'smoking gun' that medical science has been looking for to understand why these children die. "Studying this phenomenon may also provide critical insight into many other deaths, including those from SIDS and epilepsy," said Devinsky, who cofounded the SUDC Registry and Research Collaborative at NYU Langone with Gould. Further research, Devinsky notes, is also needed to determine precisely how seizures with or without fever may induce sudden death. Previous research in epilepsy patients, he says, points to difficulty breathing that is known to occur immediately after a seizure and that can lead to death. This has been found to happen more frequently in epilepsy patients, as it does in the children involved in the study, while they are sleeping face down on the stomach and without anyone witnessing the death. Continuous monitoring of child deaths and improvements in health records to track how often these convulsive seizures precede death, he explains, will be needed for this to be confirmed. Seizure-related deaths are underreported in both people with and without epilepsy. For the study, experts in forensic pathology, neurology, and sleep medicine analyzed each recording for video quality, sound, and motion. From this, they were able to determine which toddlers showed signs of muscle convulsions as a sign of seizures prior to their death and when. Access to the videos was and remains strictly limited to the researchers involved in the study. Funding support for this study was provided by SUDC UK, FACES at NYU Langone Health, and the SUDC Foundation. Additional funding support was provided by the National Center for Advancing Translational Sciences and National Institutes of Health grant UL1TR001445. Besides Gould and Devinsky, other NYU Langone researchers involved in this study are Codi-Ann Reid, BS; and Alcibiades Rodriguez, MD. Co-investigators of the SUDC video study group are Alison Krywanczyk, MD, at the Cuyahoga County Medical Examiner's Office in Cleveland; Kristen Landi, MD, at the New York City Office of the Chief Medical Examiner; Melissa Guzzetta, DO, at the Office of the County Medical Examiner in Middlesex, N.J.; Heather Jarrell, MD, at the Office of the Medical Investigator, University of New Mexico, in Albuquerque; Kelly Lear, MD, at the Arapahoe County Coroner's Office in Centennial, Colo.; Tara Mahar, MD, and Katherine Maloney, MD, at the Erie County Medical Examiner's Office in Buffalo, N.Y.; Declan McGuone, MBBCh, at Yale University in New Haven, Conn.; Alex Williamson, MD, at Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.; Katheryn Pinneri, MD, at the Montgomery County Forensic Service in Conroe, Texas; and Victoria Delavale, MPH, and Daniel Friedman, MD, at NYU Grossman School of Medicine. Media Inquiries: David March 212-404-3528 [email protected] SOURCE NYU Langone Health System