The 2025 International LGMD Conference, hosted by the Speak Foundation, was attended by over 500 LGMD patients and family members, clinicians, and scientists. For the first time, the conference included a scientific poster session for researchers to present their basic, translational, or clinical research related to LGMDs. Twenty-five abstracts were selected for presentations, including seven that were highly relevant to calpainopathy (LGMD2A/R1). Coalition to Cure Calpain 3 (C3) was proud to provide Travel Awards to facilitate the attendance of four trainees so they could present their early-stage, promising work in Orlando.
Poster Award Winners
Note: clicking on the poster titles links to high-resolution PDFs of the posters.
Improving genetic diagnosis of LGMDs using a new method of DNA sequencing
Christine Bruels (U. Minnesota), Hannah Littel, Carrie Walls, Seth Stafki, Elicia Estrella, Lauren Brady, Mark Tarnopolsky, James Dowling, Carla Zingariello, Basil Darras, Partha Ghosh, Peter Karachunski, Georgios Manousakis, Randal Richardson, Louis Kunkel, Christina Pacak, Christopher Faulk, Peter Kang
This group utilized a new method of DNA sequencing to identify gene variants (mutations) in individuals who have an LGMD pattern of weakness but did not get a genetic diagnosis from traditional clinical genetic testing. They identified cryptic variants in 68 patients including six with variants in the gene for Calpain 3. This improved diagnostic capability will enable additional individuals with LGMDs to participate in clinical trials and receive clinical care targeted to their LGMD subtype.
Developing a new gene editing strategy for patients with LGMD2A/R1
Logan Gauthier (Yale U.), Shushu Huang, Kaiyue Ma, Kenneth Ng, Katherine Koczwara, Nicholas Johnson, Monkol Lek
This team developed a new method to test if specific gene variants (mutations) impact the amount of Calpain 3 in cells, which can be utilized to differentiate those variants that are disease-causing from those that are benign. They are also designing a gene editing therapy to ‘fix’ the most common gene variant that causes LGMD2A/R1, called “c.550delA.” This therapy is being tested in muscle cells that were derived from patient biopsies.
Improving gene therapy for LGMD2A/R1 patients
Ruby Goldstein de Salazar (U. of California Los Angeles), Irina Kramerova, Stephen Hauschka, Jeffrey Chamberlain, and Melissa Spencer
These researchers are developing an LGMD2A/R1 gene therapy. Because Calpain 3 is only found in skeletal muscle, the group is focused on restoring Calpain 3 specifically to skeletal muscle cells. Importantly, their gene therapy avoids expression in the heart where it could lead to toxicity. They are currently testing the therapy in mice.
Using MRI to understand muscle changes in LGMD2A/R1 and Becker Muscular Dystrophy
Kelly Rock (U. Florida); Prathyusha Bellam; Donovan Lott; Rebecca Willcocks; Alison M. Barnard; Sean Forbes; Alexa Harris; Oneema Kamal; Julia Hinkle; Claudia Senesac; Krista Vandenborne; Glenn Walter
One major challenge to clinical trials for muscular dystrophies is that the measurements commonly used are not sensitive to detecting small changes in muscle strength. This team collected data to determine if Magnetic Resonance Imaging (MRI) can measure small changes in muscle in people living with LGMD2A/R1, as well as Becker Muscular Dystrophy (BMD). They found that one MRI technique which measures the amount of fat infiltration in muscle (called “fat fraction”) is increased in people with LGMD2A/R1 and BMD, especially those who have difficulties with physical function. These findings suggest that the technique could be used to monitor the effects of experimental treatments in future clinical trials.
Additional LGMD2A/R1 Posters
Which in-clinic assessments are helpful to measure function in individuals with LGMD2A/R1
Meredith James (John Walton Muscular Dystrophy Centre, Newcastle U.)*; Lindsay Alfano(Nationwide Children’s Hospital)*, Megan Iammarino; Natalie Reash; Chris Steiner; Audrey Beale; Melissa Smith; Stephanie Hunn; Shelley Mockler, Heather Hilsden; Dionne Moat; Jassi Sodhi; Karen Wong; Emma Grover; Emma Robinson; Anna Mayhew; Michelle Eagle; Volker Straub; Michela Guglieri; Chiara Marini Bettolo; Robert Muni Lofra; Jordi Diaz-Manera; Linda Lowes *Denotes joint first author
For future clinical trials to be successful, we need to understand which assessments (tests) best measure functional changes in people with LGMD2A/R1. This group analyzed tests performed at previous LGMD Conferences as well as clinic visits to Newcastle University and Nationwide Children’s Hospital. The tests they identified not only bring us closer to developing effective treatments and trials, but also help healthcare professionals track patient symptoms and plan treatment. This work was supported in part by a C3 Research Grant.
The patient experience of living with LGMD2A/R1: Findings from a focus group
Nicole LaMarca (Sarepta Therapeutics), Tamara Wyzanski, Chloe Carmichael, Catherine Bottomley, Jennifer Levy, Monique Dabbous
The authors of this poster organized a focus group at the 2023 International LGMD Conference to explore the experiences of those living with LGMD2A/R1. Themes included diagnostic challenges, progression of symptoms, effects on quality of life, and social and emotional impact. These findings can support clinical trial design and patient-focused drug development.
Jennifer Levy (Coalition to Cure Calpain 3), Jordan Boslego, Michela Guglieri, Ann Martin, Katherine Mathews, Michele Wrubel
This poster highlights the LGMD2A/Calpainopathy Registry, a C3 initiative. This patient-reported registry has two main goals: (1) to collect data over time from individuals with calpainopathy, and (2) to support recruitment for clinical research studies. In the first year, data was entered by over 200 participants from 41 countries. The registry has also been utilized to assist with participant recruitment for three clinical studies. It can be accessed at lgmd2a.iamrare.org.