Exercise Effects in Huntington's Disease
Condition: Huntington's Disease
MeSH terms: Huntington Disease
Study type: Interventional

Summary: 
      Huntington's disease (HD) is an incurable and fatal disorder characterised by progressive
      degeneration of the basal ganglia and the cerebral cortex. Contrary to earlier thinking, HD
      is associated with abnormalities in peripheral tissues which might even contribute to brain
      pathology including muscle wasting, mitochondrial abnormalities, and impaired muscle energy
      metabolism. Mitochondrial impairment and muscle atrophy in human HD patients and murine
      models of HD are associated with altered expression of PGC-1a, a transcriptional cofactor
      that seems to regulate many, if not all of the adaptations of muscle fibres to chronic
      endurance training, and induces improved exercise performance and increased peak oxygen
      uptake. We aim at investigating whether endurance exercise has the capability of stabilizing
      and / or reversing PGC-1a dependent alterations of muscle function and structure in HD
      patients, and whether muscle training ameliorates musculoskeletal and cardiovascular
      function, as well as motor and cognitive symptoms in HD patients.
    

Detailed description: 
      Huntington disease (HD) is an incurable and fatal disorder that affects muscle function and
      leads to cognitive decline and dementia. HD was long considered a brain disorder but
      meanwhile it was shown that HD also affects other tissues such as muscle, leading to muscle
      wasting. Previous studies suggested that the muscle disorder might be caused by an impaired
      energy metabolism through mitochondrial dysfunction, which also might also contribute to
      brain pathology.

      In muscle tissue of healthy persons, a protein named PGC 1- α seems to regulate many, if not
      all of the adaptations of muscle metabolism and mitochondrial biogenesis to chronic endurance
      training. It was shown that PGC 1- α is reduced in muscle tissue of human HD patients and
      animal models of HD.

      We aim investigating whether endurance exercise has the capability of stabilizing and / or
      reversing PGC-1α dependent decline of muscle function and structure in HD patients, and
      whether muscle training ameliorates muscular and cardiovascular function, as well as
      coordination and cognitive decline in HD. To this end, we will train 20 male HD patients
      using a 6 months progressive endurance exercise program. In order to compare the size effect
      of exercise between HD patients and healthy individuals, 20 age-matched healthy males will
      perform the identical exercise regimen as HD patients. Within one week before the training
      period starts and within one week after it has ended, we will assess metabolic and functional
      data. In addition, we will analyze muscle tissue samples for muscle fiber structure,
      metabolic phenotype and cellular pathology. Finally, gene and protein expression analyses
      will be performed on muscle tissue extracts to gain insights into the molecular regulation of
      training adaptations in HD.
    

Intervention name(s): Exercise training
Intervention type(s): Behavioral
Intervention description(s): 6 months of exercise training (2 times 30 min per week) starting one week after a 6-months natural course observation period
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment