HSØ Patient-derived iPS cells for investigating pathogenetic mechanisms of brain diseases that cause movement disorders
Dystonia is the second most common hyperkinetic movement disorder (about 1500 case in Norway), can strike at all ages, and is clinically and etiologically heterogeneous. It is characterized by repetitive, involuntary movements which often lead to abnormal postures, accompanied by significant disability, pain, and reduced quality of life and societal participation.
Mutations in several genes have been implicated in familial, primary dystonia. Several gene mutations have also been identified in dystonia-plus syndromes, such as the levodopa-responsive dystonia and myoclonus-dystonia and the paroxysmal dyskinesia syndromes. At present 16 genes with mutations causing Mendelian forms of dystonia are known, most of them with an autosomal dominant inheritance pattern.
Along with a continued search for new dystonia genes, an important challenge is to apply this genetic information in neurobiological studies of pathogenetic mechanisms, with the aim of developing preventive and more targeted therapeutic strategies. A promising method that can translate information about gene mutations into platforms for the study of living cells, is induced pluripotent stem cell (iPS cell) technology. Here, fibroblasts of dystonia patients are first transformed into iPS-cells, and these are then differentiated into the neuron types affected by the mutations. The biochemical and neurophysiological properties of these neurons can then by studied to elucidate pathogenetic mechanisms.
The principal aims of this translational project are to: 1) Build up a large Norwegian clinical database and biobank of dystonia patients, with characterized mutations, 2) Derive iPS cells from patients with identified genetic mutations, differentiate these into key neuron subtypes involved in dystonia, and characterize at molecular, cellular, and synaptic levels, 3) Uncover new disease causing mutations in Norwegian families with dystonia by combining next-generation sequencing techniques and family linkage studies.
- Lagret: 2014/166
- Biobanknummer: 511200-005
- Ansvarlig: Joel Glover
REK - Ja 1 fil
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Tidspunkt for anonymisering og sletting av dataene
- Anonymisering: november 2014
- Sletting: november 2039