Gene and Cell Based Therapy
Current surgical intervention to treat intervertebral disc degeneration (IDD) addresses the resultant biomechanics of degeneration but neglects the underlying pathophysiology of disease. Gene and cell based therapies have the potential to address the imbalance between catabolism and anabolism that occurs within the disc tissue, thus potentially augmenting the course of IDD. The laboratory has continued to make progress in the area of gene and cell based therapy for the treatment of IDD.
Recent in vivo progress using gene therapy has yielded promising results. Using a rabbit model for degeneration, potentially therapeutic genes BMP-2 and TIMP-1 have been introduced to the intervertebral disc using an adeno-associated virus vector, resulting in delay of the degenerative cascade. Ongoing projects to better regulate TIMP-1 expression using novel response elements are being conducted in collaboration with Dr. Bing Wang.
Biology of Disc Degeneration
The overall goal of Dr. Vo’s research is to understand the mechanisms of degeneration of matrix in the intervertebral discs and explore therapeutic strategies to minimize disc matrix loss. Our projects focus on investigating at the molecular and cellular levels how aging and tobacco smoking contribute to the loss of disc matrix. To achieve these goals, we collaborate with Dr. Laura Niedernhofer to use the novel progeroid mouse model (Ercc1-/∆ mice), which age rapidly due to a defect in repair of DNA damage. We also collaborate with Drs. Steven Shapiro, Peter Di, and Rocky Tuan to explore the mechanism of smoking-induced IDD. Dr. Sowa also continues to examine the potential benefit or detriment of commonly used oral supplements, such as glucosamine, chondroitin, and omega-3 fatty acids funded through NIH/NCCAM.
Dr. Gwendolyn Sowa continues to investigate how serum concentrations of certain biomarkers correlate with the presence and severity of IDD. Current interests include examining potential superiority to imaging based findings in predicting pain and pain related disability, as well as response to activity and other treatment modalities. New avenues of research include utilizing serum-based biomarkers in conjunction with imaging biomarkers to predict individual responses to treatments, such as interventional spine procedures.
Dr. Sowa also continues to explore the effects of mechanical loading in a novel ex vivo intervertebral disc testing system, which maintains biologic activity. Dr. Robert Tisherman is working on extending the capabilities of the system to include small animal models. Our goal is to gain a better understanding of the biochemical processes that occur with loading to inform future motion based therapies to facilitate healing and/or regeneration of the intervertebral disc.