Limb-Girdle Muscular Dystrophy (LGMD) 2B (Dysferlinopathies)
Limb-girdle muscular dystrophy (LGMD), a group of uniformly progressive muscular dystrophies characterized predominantly by proximal weakness affecting the pelvic and shoulder girdles and usually sparing the face. This group of disorders, recently re-classified based on the genetic underpinnings of diseases, are categorized by inheritance pattern: dominantly inherited forms (i.e., LGMD1) and those with recessively-inherited forms (i.e., LGMD2B).
The age of onset, severity, and features of LGMD vary among the subtypes. Overall LGMD affects men and women equally. LGMD patients typically suffer from:
- Skeletal muscle weakness or compromised function in identifiable, specific muscles
- Skeletal muscle immune cell invasion in identifiable, specific muscles; and
- Skeletal muscle deterioration in identifiable, specific muscles with insufficient muscle regeneration
We are now investigating Resolaris in patients with LGMD2B, a recessively inherited LGMD, often termed dysferlinopathy, given that the causative mutations reside within the dysferlin gene (DYSF).
There are multiple lines of evidence supporting a prominent role of inflammation in the pathophysiology of LGMD2B. Patients with LGMD2B possess a dysregulated immune response, including immune cell infiltration into affected muscle, increased expression of pro-inflammatory cytokines and altered cellular responses.
Based on a prevalence rate of 1:20,000, we estimate that LGMD affects an estimated 16,000 patients in the U.S., approximately 3,000 of whom have LGMD2B.
No definitive treatments exist for LGMD2B or any of the over 30 forms of LGMD.