The McColl-Lockwood Laboratory for Muscular Dystrophy Research focuses on translational research on muscular dystrophy, specifically limb-girdle muscular dystrophy (LGMD) and Duchenne muscular dystrophy (DMD). These diseases are caused by genetic defects (gene mutations) that disrupt normal muscle functions, resulting in weakening of muscle strength with fatal consequences. Currently, there is no cure or effective treatment for LGMD and DMD. The goal of the Laboratory is to develop novel therapeutic approaches for the treatment of the diseases. The Laboratory has made major progress in the areas of antisense therapy, gene therapy and new drug development and pre-clinical testing. To facilitate the process, multiple collaborations with internationally renowned laboratories have been established. Great effort has been made and will continue to be made to translate potential therapies to clinical trials.
Mission Statement: To develop therapeutic approaches for the treatment of the muscular dystrophies and to facilitate the translation of experimental therapies to clinical trials for improving the quality of life for patients with muscular dystrophy.
History of the Laboratory
The McColl-Lockwood Laboratory, directed by Qi Lu, MD, PhD, is part of the Neuromuscular/ALS Center in the Department of Neurology, which provides service to patients in the region and beyond. The Laboratory, located on the 5th floor of Cannon Research Center, was formally opened at the beginning of 2006 with the Carolinas Muscular Dystrophy Research Endowment, which was created by the McColl and Lockwood families, as well as the Carolinas HealthCare Foundation. Since then, the Laboratory has expanded significantly both in research facilities and in scientists, and now has more than 2,000 square feet of laboratory space and 10 research scientists. In addition to support from the Endowment, the Laboratory also receives funding from the Muscular Dystrophy Association, U.S. Department of Defense, North Carolina Biotechnology Center and other foundations.
Research Summary
The Laboratory is at the forefront of translational research for muscular dystrophies internationally, specifically, in the area of antisense therapy for DMD, gene therapy and drug development for different forms of muscular dystrophies.
Antisense oligonucleotide therapy uses fragments of gene sequence to target specific regions (called exons) of the human dystrophin gene. This removes the defective part of the dystrophin gene and restores the expression of dystrophin protein which is missing in the DMD patients. In 2003, Dr Lu first demonstrated the therapeutic potential of antisense therapy for DMD in vivo. Since then, much further progress has been made. The laboratory has demonstrated restoration of dystrophin expression in a murine model of DMD in muscles throughout the body by means of systemic delivery of antisense oligomers. Long-term maintenance of dystrophin expression and functional improvement of muscles can also be achieved. The results have been published in several prestigious journals, including PNAS [Proceedings of the National Academy of Sciences, USA] (2005) and Nature Medicine (2003 and 2006). Clinical trials are being planned. More recently, full restoration of dystrophin in all body muscles, including heart muscle has been accomplished.
The laboratory has also made significant progress in non-virus mediated gene therapy. Considerable improvement in delivery efficiency has been achieved with natural and synthetic polymers in both cell culture and animal models in vivo. Programs for drug screening and design have been established to identify and develop candidate pharmaceutical agents for treating the diseases. Promising lead compounds have now been identified for enhancing glycosylation, improving muscle repair and for correcting nonsense mutations.
Laboratory Members
Qi Lu, MD, PhD, Director
Ehsan Benrashid, Research Technician II
Yiumo Michael Chan, PhD, Senior Scientist
Timothy Doran, Research Technician II
Yihong Hu, PhD, Research Fellow
Elizabeth Keramaris-Vrantsis, Research Technician III
Pei Lu, Laboratory Supervisor
Jeannie Maggio, Staff Assistant
GuQi Wang, PhD, Research Faculty
Bo Wu, PhD, Research Faculty
XiaoHua Wu, MD, PhD, Research Faculty
Contact Information: Jeannie Maggio; Qi Lu
