1) Determine the sarcomeric function in muscle fibers from FSHD patients2) Determine whether sarcomeric dysfunction is specific for FSHD or is part of a generalized pathology common to muscular dystrophies3) Test new therapeutic strategies (in vitro…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in maximal forcegenerating capacity between patients with FSHD,
myotonic dystrophy type 1, oculopharyngeal muscular dystrophy and healthy
controls.
Secondary outcome
1) Muscle fiber mechanisms: cross-bridging cycling kinetics (a measure of
actin-myosin interaction dynamics), myofilament calcium sensitivity en passive
force generation.
2) Amount and structure of myofilaments: heavy chain myosin, actin, titin,
nebulin and regulatory proteins.
3) Structure of muscle fibers: histology, (ultra)structure, myofilament lattice
spacing.
These parameters will be compared between the groups included (FSHD, myotonic
dystrophy type 1, oculopharyngeal muscular dystrophy and healthy controls).
Background summary
A hallmark feature of FSHD is muscle weakness, which greatly affects the daily
life-activities of patients. Until now research on FSHD has focused mainly on
the molecular-genetic aspects underlying the disease, whereas the pathology of
the contractile machinery within the muscle fibers has recieved only very
little attention. Consequently, the pathogenesis of muscle weakness in FSHD
remains largely unknown. Our hypothesis is that dysfunction of sarcomeric
proteins plays an important role in the pathogenesis of muscle weakness in
FSHD.
Study objective
1) Determine the sarcomeric function in muscle fibers from FSHD patients
2) Determine whether sarcomeric dysfunction is specific for FSHD or is part of
a generalized pathology common to muscular dystrophies
3) Test new therapeutic strategies (in vitro) targeted at restoring muscle
function in FSHD
Study design
In vitro case-control study and in vitro intervention study.
Study burden and risks
Two visits will be needed to perform this study. One visit to the outpatient
clinic of Neurology (Nijmegen) with usual history taking, testing of muscle
strength, a venipunction, two needle muscle biopsies (8x7x5 mm), a MRI/MRS
(magnetic resonance imaging/ magnetic resonance spectroscopy) of the right
upper leg and a physiotherapeutic assessment of physical activity. Another
visit to the Department of Physiology of the Radboud University Nijmegen
Medical Centre in Nijmegen is needed to perform qualitative muscle studies. All
tests of sarcomere function will be performed in vitro. Quantitative muscle
studies can cause short term muscle pain. The risks of participation are
negligible because of the extensive skills of the performing neurologists
(prof. dr. G.W.A.M Padberg and prof. dr. B.G.M. van Engelen). Muscle biopsies
have to be performed in the target population (patients with FSHD, DM1, OPMD
and healthy controls) because it is impossible to study the pathophysiology of
muscle weakness in these patients and to develop new therapeutic strategies for
these patients without performing muscle biopsies.
Reinier Postlaan 4
6525 GC Nijmegen
NL
Reinier Postlaan 4
6525 GC Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Genetically confirmed FSHD type 1, myotonic dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OMPD). For healthy controls: no history of neuromuscular disease.
Exclusion criteria
History of cancer, use of corticosteriods during more than 2 weeks in the last 5 years, diabetes mellitus, chronic obstructive pulmonary disease, chronic heart failure pregnancy, comorbidity with influence on muscular function and contra-indications for MRI.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35549.091.11 |