“We believe that the absence of tools to measure disease progression is a major barrier to conducting drug trials in this underserved population,” Nicholas Johnson said. “This is critically important given the exciting progress in gene therapy. “We are focused on developing these tools, with a particular focus on those assessments that may be used across different LGMD types, and which assessments are unique to specific subtypes. Progress in these areas is best suited for a research network that is geographically distributed and includes investigators with varied expertise in clinical and laboratory methods.”

The Muscular Dystrophy Association awarded an MDA clinical research network grant to Nicholas Johnson, vice chair of research and associate professor of neurology at Virginia Commonwealth University in Richmond, to establish the Limb-Girdle Muscular Dystrophy (LGMD) Clinical Research Network.

The investment, totaling $700,000 over two years, supports seven centers with expertise in LGMD research and clinical care and is targeted to facilitate the development of tools and infrastructure needed to efficiently and effectively conduct clinical trials and accelerate treatments for LGMD.

Therapy development in LGMD can significantly benefit from rich natural history data to describe the clinical course of the different forms of LGMD, as well as from validated clinical outcome assessments which can be used to determine whether a drug or intervention has provided treatment benefit.

Through the coordinated activities and enhanced communication among this new network of LGMD clinics, Johnson and colleagues aim to standardize approaches and develop the clinical outcome assessments to be for used in future clinical trials.

If successful, the LGMD Clinical Research Network could facilitate the development and testing of a number of promising new LGMD therapeutic approaches.

“We are grateful to MDA for its support of this extremely important work,” Mary Reilly said. “The results from our pilot study of an MRI neuromuscular protocol in CMT1A are promising and we anticipate we will be able to confirm responsiveness with a refined protocol in children with CMT1A and in the other three common types of CMT.”

Mary M. Reilly, professor of clinical neurology and consultant neurologist, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, was awarded an MDA human clinical trials grant totaling $1 million to evaluate a new magnetic resonance imaging (MRI) protocol designed to detect disease-related changes in muscles over time in Charcot Marie Tooth disease (CMT).

In CMT, damaged motor nerves are unable to send adequate signals to muscles. This leads to muscle weakness and wasting, as well as other abnormal changes including the accumulation of fat in muscle tissue, which can be detected by MRI.

Reilly’s team has developed an MRI protocol to measure fat accumulation in thigh and calf muscles. In a pilot study to determine the protocol’s effectiveness at measuring fat infiltration in adults with CMT1A, Reilly’s team showed that the presence of calf muscle fat increased significantly over a 12-month time period.

With the new MDA funding, the team will work to refine the new protocol to include foot muscles, which could make it effective in mild cases of CMT where fat accumulation occurs more often in the feet than in calves. The team will study the refined protocol in children with CMT1A, as well as in the other three most common types of CMT: CMT1B, CMT2A and CMTX.

If successful, Reilly’s work could result in a sensitive, validated outcome measure in multiple forms of CMT, in both children and adults, that could allow researchers conducting clinical trials to reliably detect any positive effects of a candidate treatment within a 1- to 2-year timeframe.

“Meetings with industry leaders, advocacy groups and FSHD researchers have identified several gaps in our clinical trial arsenal and have pinpointed clinical trial planning as a major goal for the community,” Jeffrey Statland, M.D., said. “Not only will the FSHD CTRN help close gaps in trial readiness, but a network of sites will be created with a centralized streamlined regulatory process, specific common expertise in FSHD and an engaged patient population ready to conduct efficient, high-quality clinical trials.”

Jeffrey Statland, assistant professor of neurology at University of Kansas Medical Center in Kansas City, was awarded an MDA clinical research network grant totaling $1.2 million to expand the facioscapulohumeral muscular dystrophy (FSHD) Clinical Trial Research Network.

With colleagues, Statland is building a team of trained clinical evaluators who will all work with standardized approaches and developing regulatory strategies optimized to streamline high-quality drug trials.

The network will help ensure that clinical trials can be conducted quickly and efficiently to test potential treatments coming out of a rapidly growing pipeline of FSHD drugs in development. Ultimately, it may speed therapy development for FSHD.