MD, PhD Student Section Neuromuscular Diseases
Department of Neurology and Neurosurgery
email
s.piepers-2@umcutrecht.nltel +31-88-75 59111, pacer 1641
SupervisorsL.H.Van den Berg, E.Lindeman, S.Kalmijn
Projects
- Non invasive ventilation at home: effects in patients with amyotrophic lateral sclerosis (ALS) and their caregivers
- Histone deacetylase (HDAC) mediated regulation of survival motor neuron gene expression: a new therapeutic target for ALS
Aims
- To investigate the effects of non-invasive ventilation in ALS patients on quality of life, survival, cognition and in caregivers on quality of life. An analysis of the costs will be made. Determinants of stopping with non-invasive ventilation will be investigated.
- To investigate the effects on survival of HDAC inhibitors in a transgenic mouse model of ALS.
Summary
1. ALS is characterised by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS can occur at any age, with a median onset in the mid-fifties. Approximately 50% of the patients die within 3-4 years after the diagnosis. Respiratory failure by paralysis of respiratory muscles, is the most common cause of death. Cure is not a realistic option in ALS. Therefore treatment should be adjusted to the needs of the individual patient. A randomised, controlled trial will be performed. The principal inclusion criteria are definite or probable ALS and no signs of nocturnal hypoventilation. Randomisation will be applied for 2 treatment arms. In the first treatment arm patients will receive standard palliative treatment. In the second treatment arm, patients will receive standard palliative treatment including non-invasive ventilation. Eighty patients will be randomised, 40 patients in each treatment arm. The primary endpoints are quality of life of the patient and survival. After randomisation patients will receive questionnaires measuring the parameters. Every three months patients in both treatment arms will receive the questionnaires. One week after sending, a nurse from the Centre for Home mechanical ventilation Utrecht will visit the patient. 6 months after inclusion of the 80th patient the study will be terminated.
2. There is substantial evidence for a genetic contribution to the pathogenesis of sporadic ALS. Based on results from previous research it is hypothesised that survival motor neuron gene confers protection to motor neurons and agents which stimulate SMN expression, such as HDAC inhibitors, could extent survival. The therapeutic efficacy of HDAC inhibitors will be tested in a double transgenic mouse model of ALS. Double transgenic mice will be treated with HDAC inhibitors. Mice will be randomised to a group, receiving placebo and to one group receiving a HDAC inhibitor. Mice will be clinically monitored. Survival will be measured. The effect of these drugs on the SMN expression and the number of motor neurons at the level of the lumbar spinal cord will be determined.