Limb Girdle Muscular Dystrophy with FKRP deficiency

Research Pre-clinical phase Phase I or I/II  

Limb Girdle Muscular Dystrophy R9 (LGMDR9) or 2I (LGMD2I) is an autosomal recessive disorder caused by abnormalities in the FKRP gene, located on chromosome 19 and encoding the FKRP (Fukutin-Related-Protein) protein. FKRP protein contributes to the stability and strength of muscle tissue. It acts on alpha-dystroglycan, a key elements of the link between muscle cells and their environment.

Mutations in the FKRP gene range from mild to late-onset LGMDR9 to an earlier, more severe, and more rare form of congenital muscular dystrophy (CMD), including Walker-Warburg syndrome and muscle-eye-brain disease (MEB), with brain and eye abnormalities. LGMDR9 is a heterogeneous disease whose age of onset varies from early childhood to early adulthood. The disease is characterized by rapid deterioration and loss of mobility in adolescence or later in adulthood. It may be accompanied by respiratory distress and/or cardiac symptoms.

FKRP-deficient myopathy is particularly common in northern Europe, but is universal and is probably one of the most common Limb Girdle Muscular Dystrophy (ORPHA: 34515).

To date, there is no specific treatment for LGMDR9.

 

Genethon is a leader in the field of research regarding Limb Girdle Muscular Dystrophy R9. the Progressive Dystrophy Laboratory’s team showed proof of principle that gene therapy treatment is likely to stop the evolution of the disease. The results of this work are fundamental to develop a product to treat patients with this condition.

Today, this project is at the preclinical development stage to evaluate the effectiveness and safety of the product before administering this treatment for the first time to human.

In parallel, Genethon launched in 2019 a natural history study in three countries (Denmark, France and United Kingdom) to better understand the disease. This study will consist in following for two years the evolution of the disease in about sixty patients. To date, this study appears to be a prerequisite for the implementation of a Phase I/II gene therapy clinical trial for Limb Girdle Muscular Dystrophy R9.