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.
The Ferguson Laboratory continues to be active in spinal biomechanics research, which is directed by Kevin Bell, PhD. Clinical and laboratory based experimentation focuses on assessing the effects of joint injury, repair, and rehabilitation to promote more effective clinical treatments and improved clinical outcomes. Novel experimental techniques including a robotic testing system, virtual reality assisted motion tracking, and wireless joint function assessment are utilized to answer clinically relevant research questions. Recent projects have focused on improved compressive loading methodologies for cervical spine flexibility testing, development of a clinically motivated scoliosis testing platform, and validation of a wearable remote rehabilitation system.
The group is also working to develop an mHealth Technology to maximize participation in and adherence to total knee replacement (TKR) rehabilitation. This project builds upon the early success in the development of interACTION (patent pending), a wearable joint rehabilitation system that won the 2013 Big Idea Competition and received pilot funding from the Coulter Foundation and NIH funding from PInCh – Pittsburgh Innovation Challenge (Under the CTSI parent grant #UL1TR000005, PI: Dr. Steven Reis).