Project 458799

Intervertebral discs (IVD) are rings of cartilage found in the spine between the vertebrae. Their degeneration is one of the major causes of back pain, a condition that represents a serious socio-economic burden. Upon degeneration, the IVDs become inflamed, and this creates an environment which has been associated with pain. Although new treatments have significantly improved over the past decades, patients presenting with advanced stages of this disease require invasive surgery to relieve pain. It has recently been found that the accumulation of these abnormal (senescent) cells causes IVD degeneration by releasing substances that cause inflammation. Thus, selectively removing these abnormal cells has been proposed as a novel therapeutic target for IVD degeneration. The goal of this research is to use an animal model to evaluate if the compounds o-Vanillin and the FDA approved RG-7112 can target and/or remove these abnormal cells (i.e. senolytic compounds) thereby resulting in the treatment of IVD degeneration and low back pain. Using mice lacking the secreted protein acidic and rich in cysteine (SPARC) gene to mimic back pain and IVD degeneration seen in patients, we aim to evaluate the role of o-Vanillin and RG-7112 administration at different stages of disease progression. This work will contribute to our understanding on IVD degeneration and can result in the identification of novel therapeutics to treat IVD degeneration and low back pain which will ultimately improve the quality of life for millions of individuals worldwide and will reduce the number of invasive procedures performed on a yearly basis.