Assess the mtDNA mutation load in mesoangioblasts of mtDNA mutation carriers

Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS)
due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency
1/5,000), but severe multisystem disorders. Clinical manifestations are highly
variable, but predominantly affect energy demanding tissues, like brain and
muscle. Myopathy is a common feature of mtDNA disorders, being present in more
than 50% of the mtDNA mutation carriers, and seriously affects patients*
general well-being and quality of life. Currently, no treatment is available
for these patients, although the induction of muscle regeneration by exercise
treatment has been shown to alleviate the myopathy in patients. This implies
that the patients can produce muscle fibres, which perform better, most likely
because the mutation load is lower. This is based on the activation of myogenic
precursor cells, called satellite cells, with a very low or absent mtDNA
mutation load in these patients. In recent years, other myogenic precursors
termed mesoangioblasts have been recognized as a source for development of a
systemic myogenic stem-cell therapy and allogeneic transplantation has been
successfully applied to mice and dogs with Duchene muscular dystrophy, followed
by an ongoing trial in affected boys. For mtDNA diseases autologous stem-cell
therapy could be feasible to treat myopathy, if mtDNA disease patients would
produce mesoangioblasts without the mtDNA mutation or with a very low mutation
load. Therefore, the aim of this project is to determine the mtDNA mutation
load in myogenic stem cells (mesoangioblasts) of mtDNA disease patients and
identify the patients or mutations for which this is a feasible approach.

The primary objectives of this project are to assess the mtDNA mutation load in
carriers of a mtDNA mutation and identify patients and/or mutations with with
no/low mtDNA mutation load in mesoangioblasts. Secondary objectives aim at
determining the proliferation, myogenic differentiation and OXPHOS capacity of
mesoangioblasts.

Monocenter observation study

Participation is not result in direct benefit for the participant. The primary
benefit of this study will be about a better knowledge on the mtDNA mutation
load in mesoangioblasts, which could potentially serve as therapeutic option to
ameliorate myopathy in mtDNA mutation carriers for which currently no therapy
is available. The risk of complications associated with the muscle biopsy. In
some cases, the muscle biopsy can be painful. Infections and bleeding
afterwards are possible, but rare