Research Network Supports Limb-Girdle Muscular Dystrophy Treatment Development

To design effective clinical trials for new therapies, researchers need to know how to measure success. Several years ago, four neuromuscular researchers realized there was a gap in the knowledge needed to develop therapies for limb-girdle muscular dystrophy (LGMD). Jeffrey Statland, MD, a professor of neurology at the University of Kansas Medical Center in Kansas City, Kansas;  Nicholas Johnson, MD, an associate professor of neurology at Virginia Commonwealth University; Chris Weihl, MD, PhD, a professor of neurology at Washington University in St. Louis; and Matthew Wicklund, MD, a professor of neurology at University of Texas in San Antonio, set out to close that gap by creating a network that could improve the course of LGMD research with increased understanding of the genetics associated with different diagnoses.

LGMD is a diverse group of disorders with many subtypes categorized by the gene mutation and inheritance pattern. Together, the disorders that constitute LGMD are the fourth most common genetic cause of muscle weakness.

Identifying gaps

“Companies were starting to develop gene replacement therapies for several of the LGMDs,” Dr. Statland says. “We knew that they were working on gene replacement for most of the recessive LGMDs, and we realized we didn’t have very much natural history data.”

Without this natural history data, which shows how a disease or subtype typically progresses, researchers wouldn’t truly know if their therapy was altering the disease course.

“If there are subgroups who have different trajectories, how are you going to tell if the drugs are working? What are you going to measure?” Dr. Statland asks.

He also notes that sponsored genetic testing programs, offered at no cost through MDA Care Centers, have increased access to genetic testing. But as more genetic testing was performed, more people received results indicating variants of unknown significance (VUSs).

“Somewhere between 50% and 60% of patients will have at least one VUS, so a real gap in the field was a pathway for resolving these variants,” he says.

Finding a solution

The solution was to form the GRASP-LGMD Consortium in 2018, a network of researchers and organizations working together to develop trial endpoints and prepare sites for potential gene therapy trials for LGMD.

“We put this network together to build those tools, biomarkers, and clinical trial outcomes to understand what happens to groups that have different trajectories, and then to find a pathway to resolve people who don’t have genetic certainty yet,” Dr. Statland says.

“Often you need a collection of investigators that are capable of seeing patients close to where they are to reduce burden with people with limited travel capacity,” adds Dr. Johnson, one of the original founders of the consortium. Currently, MDA, the LGMD2i Research Fund, and CureLGMD2i Foundation are co-funding the GRASP-LGMD Consortium, along with NINDS, Sarepta Therapeutics, ML Bio Solutions, and Edgewise.

The project evolved from a few centers to 15-20 in the US and internationally. It focused on developing natural history data, biomarkers, and tools to resolve genetic variants of unknown significance. The network, including the facioscapulohumeral muscular dystrophy (FSHD) and myotonic dystrophy networks, has facilitated large-scale clinical trials and real-world study designs.

“Our goal is to reduce barriers across those LGMDs so there’s not a question about what the natural history of the disease is or what the end points would be to incentivize drug development in those disorders,” Dr. Johnson says.

Critical support

Last year, MDA awarded a Clinical Research Network Grant to Dr. Statland to help GRASP-LGMD consolidate the administration of clinical trial networks where they overlap for myotonic dystrophy, FSHD, and LGMD. “Much of the way we organize these networks is similar, so it made it easy to consolidate,” Dr. Statland says.

The LGMD2i Research Fund and CureLGMD2i then provided additional funding at the end of 2025 to lower the cost of managing clinical trial sites. “Patients with LGMDs are facing a dearth of therapeutic options,” says Jean-Pierre Laurent, Director of the LGMD2i Research Fund. “It is critical that efforts to facilitate the development of these options be coordinated and done by experts in these conditions. We hope that, by completion of this grant, we will have significantly supported these efforts.”

Virginia Commonwealth University (VCU) serves as the central coordinating site for the GRASP-LGMD Consortium, under the direction of Dr. Johnson. Dr. Statland serves as the clinical research liaison. The biorepository is under the direction of Dr. Weihl at Washington University.

“We run the central coordinating center and the data management center,” Dr. Johnson says. “The data is deposited at VCU, we steward it, make sure it’s of appropriate quality, then share it with interested parties like pharmaceutical companies or biotech. As a clinical coordinating center, our goal is to identify sites close to where patients live and fully enroll these trials. If we can enroll patients in natural history studies, that’s a strong sign to drug developers that this is a disease that’s of interest to people.”

Support from MDA and other organizations has been crucial for maintaining and training coordinators and evaluators, accelerating drug development for muscular dystrophies.