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The McColl-Lockwood Laboratory for Muscular Dystrophy Research focuses on developing novel therapies for muscular dystrophy, specifically limb-girdle muscular dystrophy (LGMD) and Duchenne muscular dystrophy (DMD).

Directed by Qi Long Lu, MD, PhD, the lab is a division of the Carolinas Neuromuscular/ALS MDA Center, part of Atrium Health Musculoskeletal Institute and Atrium Health Neurosciences Institute. The laboratory, located in the James G. Cannon Research Center, received funding from the Carolinas Muscular Dystrophy Research Endowment, Atrium Health Foundation, Muscular Dystrophy Association (MDA) and federally funded grants.

The McColl-Lockwood Laboratory has established cell cultures, specific reagents and animal models specific and critically important to therapeutic development for muscular dystrophies. The laboratory continues to make milestone achievements in experimental therapies by its research team of scientists and technicians with specialized training and experience in drug design, pharmacology, and cell and molecular biology. The laboratory includes more than 2,000 square feet of space with state-of-the-art equipment, which enables researchers to focus on cell biology, molecular biology, drug development and drug testing both in vitro and in vivo. The laboratory also has an academic association with the University of North Carolina Charlotte and Chapel Hill and trains postgraduates and other students.

Understanding Causes and Impact of Muscular Dystrophies

Limb-girdle muscular dystrophy (LGMD) and Duchenne muscular dystrophy (DMD) are caused by genetic defects (mutations) that disrupt normal muscle function, resulting in the weakening of muscle strength with fatal consequences. The FKRP gene, which provides instructions for making a protein called fukutin-related protein, is an example of a gene prone to mutation. The resulting protein is present in many of the body's tissues but is particularly abundant in the brain, cardiac muscle and skeletal muscles (those used for movement).

Mutations in the FKRP gene cause a form of congenital muscular dystrophy (CMD) or the mild, later-onset LGMD2i. Similar to all LGMDs, LGMD2i patients experience progressive muscle weakness affecting cardiac, respiratory and other skeletal muscles. The result is continuous muscle damage followed by repair, which causes the muscle to be gradually replaced by non-functional scar or fat tissue. Eventually, the muscles are no longer able to perform their function, leading to failure in mobility and respiratory and cardiac function.

The FKRP Gene Connection in Muscular Dystrophy Research

Currently, there are no approved treatments – and no cure – for LGMD and DMD. But there is hope. The goal of the McColl-Lockwood Laboratory is to develop novel therapeutic approaches for the treatment of the diseases. Since its 2006 opening, the laboratory has implemented fundamental research in several areas critical for development of experimental therapies, including a clearer picture of the FKRP gene and its functions.

After decades of research, scientists understand the precise mechanism of action for the FKRP. Working with more than 10 other genes, FKRP adds a sugar chain (glycan) to the protein called alpha dystroglycan (a-DG) located at the surface of the individual muscle fibers which form muscle mass. This glycan is important for muscle fibers of both skeletal and cardiac muscles to link with surrounding connective tissue, preventing damage during contraction. As a result of defect in FKRP (and other related genes), levels of the glycan will be greatly reduced, leading to weakening or loss of the link between fibers and connective tissues. Consequently, the diseased muscle fibers suffer much greater tear and damage than normal muscle fibers (beyond the degree our muscle can repair) when we exercise either voluntary (controlled) or involuntary (automatically, as is the case with the cardiac muscle) muscles.

Animal Model Creation in Muscular Dystrophy Research

The McColl-Lockwood Laboratory has established several animal models of muscular dystrophies and cell lines representing the diseased muscles from patients with different degrees of severity. These models are essential for testing of therapies.

With the establishment of mouse models bearing the same mutations detected in patients with FKRP mutations, including the common L276I mutation representing mild and moderate LGMD2i and less common P448L mutation associated with more severe disease manifestation of CMD, experimental therapies have been developed in the McColl-Lockwood Laboratory. Currently, two therapeutic approaches, AAV gene therapy and a metabolite ribitol-mediated treatment, are under development for clinical trials to LGMD2i.

The laboratory has also established various vectors representing normal and mutated FKRP genes for functional and therapeutic study. Specific antibody against FKRP protein has been raised and drug screening protocol has been established for identifying candidate compounds to rescue the glycosylation defects and to prevent muscle damage.


Meet the Team

Selected Publications

Dhoke NR, Kim H, Selvaraj S, Azzag K, Haowen Zhou HW, Oliveira NAJ, Tungtur S, Ortiz-Cordero C, Kiley J, Lu QL, Bang AG, Perlingeiro RCR. A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Cell Rep. 2021 Jul 13;36(2):109360

Lu QL. Revertant Phenomenon in DMD and LGMD2I and Its Therapeutic Implications: A Review of Study Under Mentorship of Terrence Partridge. J Neuromuscul Dis. 2021 Jun 17. doi: 10.3233/JND-210692.

Lu PJ, Tucker JD, Branch EK, Guo F, Blaeser AR, Lu QL. Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth. Sci Rep. 2020 Mar 18;10(1):4935. doi: 10.1038/s41598-020-61747-z.

Karim Azzag , Carolina Ortiz-Cordero , Nelio A J Oliveira , Alessandro Magli , Sridhar Selvaraj , Sudheer Tungtur , Weston Upchurch, Paul A Iaizzo , Qi Long Lu , Rita C R Perlingeiro. Efficient engraftment of pluripotent stem cell-derived myogenic progenitors in a novel immunodeficient mouse model of limb girdle muscular dystrophy 2I. Skeletal Muscle. 2020 Apr 22;10(1):10

Contact Information


James G. Cannon Research Center
Atrium Health Carolinas Medical Center
1000 Blythe Blvd., Charlotte, NC 28203

Phone Number:
(704) 355-4519

Fax Number:
(704) 355-1679