Clinical Trial: Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin

Brief Summary: Dysferlin is a protein with an important role in the repair of muscle surface membranes. Mutations in dysferlin cause different forms of muscular dystrophies. Dysferlinopathies are inherited in an autosomal recessive manner, and many patients with this disease harbor mis-sense mutations in at least one of their two pathogenic DYSF alleles. These patients have significantly reduced or absent dysferlin levels in skeletal muscle, suggesting that dysferlin encoded by mis-sense alleles is rapidly degraded by the cell's quality-control system. In a series of in-vitro experiments we showed that mis-sense mutated dysferlin can be salvaged from degradation by proteasomal inhibition. This resulted in an increase of functional dysferlin protein and a subsequent repair of plasma membranes of cultured patient-derived muscle cells. In this proof-of-concept study we would like to test wether proteasomal inhibition can salvage mis-sense mutated dysferlin in patients harboring certain dysferlin mis-sense mutations.

Detailed Summary:
Sponsor: University Hospital, Basel, Switzerland

Current Primary Outcome: Dysferlin protein expression levels change from baseline over 5 days assessed by repeated biopsies and blood draws in skeletal muscle and in blood monocytes following administration of a single dose of Bortezomib. [ Time Frame: repeated needle muscle biopsies over a five day period ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University Hospital, Basel, Switzerland

Dates:
Date Received: April 29, 2013
Date Started: December 2012
Date Completion: July 2017
Last Updated: May 12, 2017
Last Verified: May 2017