Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Parkinson disease (PD) is characterized clinically by motor dysfunction; resting tremor, slowness of movement, stiffness and loss of balance. Initially, the symptoms are insidious and typically asymmetric, and most patients suffer an unstoppable decline. The main drug treatment is L-dopa which helps the motoric symptoms but fails to halt the progression of disease. The most common pathogenic mutation that causes sporadic and familial PD is LRRK2 (Leucine-rich repeat kinase 2) p.G2019S. LRRK2 mutations accounts for up to 40% of sporadic PD in Tunisia. Preliminary results from my project have shown that some LRRK2 p.G2019S patients have very early-onset (<40 years) disease while there are also elderly asymptomatic carriers and very late-onset patients (>76 years of age or onset).Thus, genes other than LRRK2 p.G2019S are believed to affect the clinical variability seen in these PD patients. Identifying modifier genes will provide insight into the biological mechanisms of PD and provide novel therapeutic targets for PD. I hypothesize that there is a genetic modifier that can modulate the age of onset of LRRK2 p.G2019S carriers.