The ability to harness genomic technologies to provide a more accurate diagnosis for diseases in children needs to be accompanied by treatments that are also tailored to the individual patient. Many medications available to treat newborns, infants, children and adolescents have been developed primarily for similar diseases in adults, and relatively limited information is available to guide the use of these agents in children of different ages. Even less information is available to inform adjustment of doses to best treat individual children.
No Parent Thinks Their Child is Just “Average”
Existing dosing guidelines generally represent the dose that, on average, provides the desired therapeutic response for a population of patients. On the other hand, each parent recognizes that their child is special – not just “average” — and so the selection of medication and the dose of that medication should take into consideration those factors that make each child unique. Two of these factors are the child’s genetic makeup, or genome, as well as their stage of development, referred to as “ontogeny”. Multiple additional factors, such as sex, diet, lifestyle factors, other disease conditions, concurrent medications and environmental factors may also contribute to variability in the way that a child’s body breaks down medications or responds to them in terms of improvement in symptoms or the potential for side effects. The challenge is to identify as many of these factors as possible and include them in tools designed to individualize treatment for each patient.
“GOLDILOKs and Precision Therapeutics Research for Children”
To address this challenge across multiple clinical areas, the GOLDILOKs (Genomic- and Ontogeny-Linked Dose Individualization and cLinical Optimization for Kids) research program has been designed to address the concept of “Not too big, not too small … the medication and dose that is “just right” for each child”. Current programs focus on validation and refinement of an artificial intelligence-based predictor of response to selective serotonin reuptake inhibitor (SSRI) antidepressants in adolescents with depression, development of dosing tools for a medications, such as metformin used in the management of pediatric patients with insulin resistance and type 2 diabetes mellitus and pimozide used to treat Tourette syndrome, among others. A major goal of the Precision Therapeutics team is to develop partnerships with pediatric providers as well as patients and their families to integrate research activities into clinical care in a manner that is minimally disruptive to patients and families and clinic flow. The ultimate goal of the Precision Therapeutics program is to generate new knowledge that is directly relevant to clinical care of the patient populations seen at Children’s Mercy Kansas City and beyond.