Mary Lieh-Lai, M.D., an associate professor of the Wayne State University School of Medicine's Department of Pediatrics and principal investigator for the WSU Pediatric Pharmacology Research Unit, received $243,183 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development to help fund the unit's research.
This latest grant comes under the auspices of the American Recovery and Reinvestment Act, the national economic stimulus package signed into law by President Barack Obama.
The PPRU at the School of Medicine has been in existence for 15 years now and is part of a national network of sites. Established in 1994 with funding from the Best Pharmaceuticals for Children Act adopted by Congress and signed into law by President George Bush, the PPRU network was created to allow the study of drugs in children.
"One of the major issues with drugs and children is that pharmaceutical companies hardly ever conduct trials in children for new drugs because the pediatric population is not a profitable one. Children only go up to 18 years, while adults can keep going to their 90s and even beyond," Dr. Lieh-Lai explained. "We term children as 'therapeutic orphans.' The medications we use in treating them have mostly only been studied in adults, and practitioners who work with children just reduce the adult dose based on the child's weight. There had been no considerations regarding the immature systems of children, which make them metabolize drugs differently."
With passage of the BPCA, the government offered drug-manufacturing companies a deal: If they agreed to fund trials in children, their exclusivity on larger money-making drugs would be extended by six months.
The PPRU receives funding in five-year cycles. For every cycle, the WSU PPRU receives $1.5 million to $1.9 million. Most of the money is used to fund the infrastructure to facilitate the conducting of drug trials in children and to carry out animal model research.
Each of the 13 national sites that make up the network is composed of physicians, clinical pharmacologists, biostatisticians, pharmacologists, study coordinators, research technicians and study managers. Most sites have a clinical research center equipped with beds to house patients for overnight drug studies, a laboratory to process samples and secure data, and sample storage facilities.
For the current funding cycle, WSU PPRU researchers are focusing on the use of codeine in mechanically ventilated infants; the pharmacokinetics of intravenous terbutaline in children with asthma; targeted drug delivery using dendrimers in rabbit internal jugular vein clots; biomarker-guided treatment of autism; the pharmacokinetics of morphine in children; azithromycin pharmacokinetics in neonatal infants; the pharmacokinetics of buspirone in children with autism; and bilirubin binding in neonatal infants given intravenous ibuprofen for treatment of patent ductus arteriosus.
"We already have some preliminary results that indicate that children handle these drugs differently than adults," Dr. Lieh-Lai said. "These studies will help us determine the best way to treat children and avoid adverse drug effects based on knowledge obtained from trials that were actually done in children. Children are often neglected in the medical world that is dominated by adults. The efforts and studies conducted by the NICHD PPRU network will help change that."
Over the 15-year history of the network, she said, the PPRU has conducted hundreds of drug trials in children, including the use of analgesics, antibiotics, anti-hypertensives and sedatives. Research in the unit has included genetic polymorphisms, age-related differences in drug metabolism, and pathogenesis of autism and its treatment.
"We have been very successful in investigating targeted drug delivery using dendrimers and nanoparticles in animals. The funding has helped us establish several animal models - such as a mouse model of asthma, rat model of pain, rabbit model of jugular vein clot and rabbit maternal chorioamnionitis," she said. Funding for these pilot animal studies helped the PPRU establish a "close working relationship" with the Wayne State University Departments of Chemical Engineering, Occupational and Environmental Health Sciences, the School of Pharmacy and the Perinatology Research Branch.
The work of the PPRU has also assisted junior faculty in Dr. Lieh-Lai's division secure additional grants to further research.