Investigations: A Compendium of Research Under Way at UH Rainbow

Innovations in Pediatrics - Spring 2016 Download PDF

Novel Respiratory Stimulant in Preclinical Testing

A novel compound that stimulates respiratory drive – an urgent need in perioperative, critical care and trauma/battlefield settings – is in preclinical testing at UH Rainbow Babies & Children’s Hospital, thanks to research by pediatric pulmonologist Benjamin Gaston, MD.

Respiratory depression, most commonly caused by drugs used for pain relief and sedation, can result in death or mean that patients require prolonged mechanical ventilation.

“A respiratory stimulant could be lifesaving,” says Dr. Gaston, who serves as Division Chief of Pediatric Pulmonology at UH Rainbow Babies & Children’s Hospital. “The principal effective current therapy is positive pressure ventilation.” Dr. Gaston is also Professor of Pediatrics at Case Western Reserve University School of Medicine.

The compound under investigation in Dr. Gaston’s lab contains thiol, a class of organic compounds similar to alcohols and phenols, but which contains a sulfur atom in place of the oxygen atom. Dr. Gaston’s previous research has shown that thiols can accept nitrosonium ions from desaturating hemoglobin to form compounds that stimulate respiratory drive.

Initial results with the target compound, performed in close collaboration with pharmacologist Stephen J. Lewis, PhD, Professor of Pharmacology and Pediatrics at the School of Medicine, are encouraging, Dr. Gaston says.

“It stimulates respiratory drive and overcomes narcotic-induced respiratory depression. Remarkably, it does not blunt analgesia,” he says. “We anticipate that we should be able to get to quite low therapeutic doses in humans with parenteral, transdermal and/or oral preparations. We anticipate reduced hospital costs with this agent and significantly decreased mortality. We therefore believe that our novel respiratory stimulant will be a major breakthrough when it is translated into clinical practice.”

Dr. Gaston’s research is funded by the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio – part of The Harrington Project for Discovery & Development – an international initiative designed to support and encourage innovative physician-researchers who want to help expand and improve the range of medications available to patients.

To contact Benjamin Gaston, MD, email Benjamin.Gaston@UHhospitals.org.

Low-Dose Buspirone May Help Reduce Restrictive and Repetitive Behaviors in ASD

A new study suggests that low doses of the anti-anxiety medication buspirone may be a useful addition to behavioral therapy in treating young children with autism spectrum disorder (ASD). The study, published in the Journal of Pediatrics, was conducted as part of the Autism Center of Excellence Network.

“Low-dose buspirone reduced restricted and repetitive behaviors in young children with ASD,” says Max Wiznitzer, MD, a pediatric neurologist at UH Rainbow Babies & Children’s Hospital and coauthor of the study. “Therefore, this treatment might be considered for further exploration as a useful adjunct therapy to target these behaviors, in conjunction with early behavioral intervention.”

Dr. Wiznitzer is also Professor of Pediatrics at Case Western Reserve University School of Medicine.

Restrictive and repetitive behaviors among children with ASD can interfere with learning and are a major cause of family stress, research shows. They can also limit the impact of early behavioral interventions provided by ASD caregivers.

“When they can be implemented, early behavioral interventions can improve socialization, language skills and adaptive behavior in young children with ASD,” Dr. Wiznitzer says.

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial. J Pediatr. 2016 Mar;170:45-53.

To contact Max Wiznitzer, email Max.Wiznitzer@UHhospitals.org

 

Dr. Wiznitzer’s research was supported by grant funding from the National Institutes of Health to Case Western Reserve University School of Medicine.

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