Biomarker Development in LGMD 2i
Biomarker Development in LGMD 2i
The overall goal of this natural history study is to define the key LGMD2i phenotypes as
 measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker
 for LGMD 2i to support therapeutic development.
Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due
 to missense mutations in the FKRP gene. Patients develop progressive proximal muscle weakness
 that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and
 respiratory compromise.

 There are promising new therapies that have been developed and as a result therapeutic trials
 are approaching.

 The rationale for this study is to define appropriate COAs for LGMD 2i, which will facilitate
 therapeutic development and ensure properly powered clinical trials. In addition, measurement
 of dystroglycan in muscles represents a potential muscle biomarker that could be used in
 early phase clinical trials as a measure of target engagement. The clinical utility of
 changes in dystroglycan has not been validated in human samples.
Inclusion Criteria:

 -  Age between 10-65 at enrollment

 -  Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle
 pattern, or in a distal extremity)

 -  A genetically confirmed mutation in FKRP (LGMD 2i).

 -  Up to 60 participants will complete the10-meter walk test in greater than 4 seconds.

 -  Up to 40 participants will complete the 10-meter walk test in over 12 seconds.

 -  Up to 20 participants may be non-ambulatory

 Exclusion Criteria:

 -  Any other illness that would interfere with the ability to undergo safe testing or
 would interfere with interpretation of the results in the opinion of the site
 investigator.

 -  History of a bleeding disorder, platelet count <50,000, current use of an
 anticoagulant.

 -  Positive pregnancy test at time any timepoint during the trial