Researchers seek safer, more effective treatment for Down syndrome

A Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Research Starter Grant in Pharmacology/Toxicology will allow researchers at the University of Kansas and Children’s Mercy Kansas City to lay the groundwork that could make certain medications in the treatment of children with Down syndrome safer and more effective.

Down syndrome is the most common genetic cause of intellectual disability worldwide, and children who have it are at a greater risk of developing a variety of health problems, including acute lymphoblastic leukemia and juvenile idiopathic arthritis. The drug methotrexate is commonly used in the treatment of these conditions but is poorly tolerated by patients with Down syndrome, which greatly limits its use in these patients. 

“For more than 30 years, we have known that children with Down syndrome are markedly more sensitive to methotrexate and at greater risk of developing therapy-limiting toxicities,” said lead investigator, Ryan Funk, assistant professor at the University of Kansas Department of Pharmacy Practice.  “Advances in our understanding of the genetic and non-genetic determinants of methotrexate safety and efficacy are now allowing us to apply our findings toward improving the use of this important drug in the treatment of children with Down syndrome.”

 As a result, Funk is seeking novel approaches toward enhancing the tolerability of methotrexate in patients with Down syndrome to enhance its safe and effective use in this vulnerable and understudied pediatric patient population.  

Down syndrome results from a full or partial extra copy of chromosome 21 and is commonly referred to as trisomy of the 21st chromosome. As a result, Down syndrome patients have an extra copy of genes located on chromosome 21, including a number of genes that are important in the pharmacological activity of methotrexate.  In this one-year study, Investigators in Funk’s laboratory are working with collaborators at Children’s Mercy Kansas City to define the impact of trisomy of the 21st chromosome on the biochemical response to methotrexate and are using this information to design modified dosing recommendations and identify dietary supplementation approaches to prevent methotrexate toxicity in these patients.

Funk earned his Pharm.D. and Ph.D. at the University of Kansas. He most recently served as a postdoctoral fellow at Children's Mercy Kansas City in Kansas City, Missouri. His research interests include molecular mechanisms of variability in clinical response to immunologically active agents used in the treatment of pediatric autoimmune diseases. He encourages the involvement and training of pharmacy students in clinical- and laboratory-based research.