Medicine & Dentistry-Biochemistry
University of Alberta
Summary of research:
This project investigates the etiology and prevalence of a poorly understood pediatric condition for which no effective treatments exist. The disease of interest affects babies and children who can’t make enough of a protein called, MMP-2. Severe MMP-2 deficiency is rare, resulting from MMP-2 gene defects which trigger crippling arthritis, chronic pain, severe muscle damage, heart disease, and numerous other metabolic problems. Unbeknown to many, mild MMP-2 deficiency presents as a side-effect of taking medicines that inhibit MMP-2 such as doxycycline (an antibiotic) and statin (cholesterol-reducing drug). Mice lacking the MMP-2 gene are the best animal model for testing new treatments for MMP-2 deficiency. While working with MMP-2-deficient mice, we discovered high levels of a protein called ‘sPLA2’ and found that too much sPLA2 can cause inflammation in the mice. Our laboratory is exploring the mechanisms used by MMP-2 to modulate metabolism and dampen inflammation, including mechanisms involving sPLA2’. These studies could help understand how and why patients with MMP-2-deficiency suffer from arthritis. Moreover, we are also conducting to determine if alterations in MMP-2 levels associate with rheumatoid and other inflammatory forms of arthritis. We expect to learn about the prevalence of MMP-2 deficiency in patients with arthritis and if MMP-2 deficiency in these patients correlates with high sPLA2 levels or other signs of abnormal metabolism and inflammation disease. This new knowledge will help improve the treatment of patients with either MMP-2 deficiency or arthritis - many of which are children.