New guidelines for the diagnosis and management of calpainopathies (LGMD R1 and LGMD D4) have recently been published with a view to optimising clinical practice and reducing the time to diagnosis, as part of a new National Diagnostic and Care Protocol (PNDS).
- There are three main phenotypes of LGMD R1, defined according to the site of muscle involvement at the onset of the disease: the pelvi-femoral phenotype, the scapulo-humeral phenotype and hyperCKemia.
- The clinical presentation of LGMD D4 is generally milder.
- Restrictive respiratory syndrome may occur in advanced stages of the disease and require respiratory support.
- Diagnosis is based on muscle and functional assessment, measurement of serum creatine kinase levels and a muscle biopsy. It is confirmed by genetic testing.
- Management is symptomatic, focusing on maintaining motor function and rehabilitation (physiotherapy, adapted physical activity), preventing orthopaedic complications, and respiratory and cardiological monitoring.
The PNDS also reviews therapeutic strategies currently under development, including:
- Restoring calpain-3 protein expression through cell therapy combined with CRISPR/Cas9 or through gene therapy, which is currently at the preclinical stage only.
- Increasing muscle mass through the pharmacological stimulation or blockade of muscle growth factors (such as the anti-myostatin antibody MYO-029, which is being evaluated in humans).
The French national registry for calpainopathies (C3R), funded by the AFM-Téléthon, will help to improve our understanding of these diseases and prepare for future clinical trials (defining relevant evaluation criteria, identifying patients, etc.).
HAS. 2025 (in French)
