The title of the consortium reflects the genetic diversity and overlapping phenotypes in LGMD: Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD).
The limb-girdle muscular dystrophies (LGMDs) are divided into over 30 different subtypes based on a combination of the mutation type and clinical presentation. The LGMDs are progressive muscular dystrophies with no FDA approved therapies that as a group represent a large unmet clinical need. Despite the diversity in genetic and clinical presentation, the LGMDs sit at a crossroads in therapeutic development: where the technical ability to target a given mutation or pathogenic pathway has outstripped our clinical understanding of the natural history of the LGMDs. Trials of gene therapy and drugs designed to improve muscle quality or function are expected for the LGMDs in the next 5 years. Obstacles faced by the LGMD community and any rare disease community include: small, geographically distributed populations; imprecise diagnostic testing; a paucity of validated clinical trial endpoints; a need to define coherent inclusion criteria; and creation of a trained and patient-activated LGMD infrastructure for conducting clinical trials.
We have identified 5 key strategic objectives that formation of a GRASP-LGMD consortium could address or improve:
1) drug target identification and development
2) accurate diagnostic testing
3) clinical outcome assessment validation
4) patient-reported outcome validation and
5) biomarkers discovery and validation