The goal of the Genotype-specific Approaches to Therapy in Childhood (GATC) program is to prevent adverse drug reactions (ADRs) in children by identifying predictive genomic markers for these reactions. This project aims to create personalized dosing recommendations for common drugs based on a child’s genetic profile.

GATC will identify ADR predictive markers by comparing DNA and plasma samples from patients who suffered ADRs with patients of the same age who had no reaction after the same medication. The GATC will obtain its clinical material from two unique Canada-wide surveillance networks: 1) the Canada Paediatric Surveillance Program, a network of 2,300 paediatricians and 2) the GATC hospital-based active surveillance network across 10 major hospitals. “Two networks of health professionals are needed to capture ADRs” explains Dr. Carleton “because they occur in both community and hospital settings.”

Using these valuable clinical resources plus existing strengths and expertise in clinical genomics and genetics, the GATC program will apply innovative large-scale genomic and proteomic strategies to define the genes that cause, or are predictive or, childhood ADRs.

First of all, GATC will examine 500 known functional SNPs in candidate genes to find predictive markers. Base pair changes that alter drug metabolism, drug transport or other physiological pathways of ADR may be causative and therefore predict ADRs. They will also identify novel ADR-predictive SNPs by sequencing candidate genes in the patients. Furthermore, the reduced genetic heterogeneity in Canada’s unique isolated founder populations (i.e. Quebec, Newfoundland, Nova Scotia) represent a tremendous opportunity for new ADR gene discovery.

Proteomic analysis will complement the above genome studies because GATC hypothesizes that children susceptible to ADR will have protein biomarkers apparent in their plasma.

Pharmacokinetic studies will be done to validate the novel ADR predictive SNPs and mutations. Pharmacokinetic analysis will also be used to characterize possible ADR mechanisms by determining drug concentrations in patients.

The post-genomic era represents an unprecedented opportunity to prevent ‘unavoidable ADRs’ by translating our increasing genomic and proteomic knowledge into tools that impact the care and treatment of children. Armed with new predictive knowledge of a child’s genomic ADR risk profile, GATC will provide a cost-effective prevention strategy to reduce the incidence of childhood ADRs. The outcomes of the project could influence paediatric medical practices around the world.