ATP correlation in PD
Does mitochondrial function correlate in brain tissue and peripheral tissue in patients with Parkinson’s disease and controls?
Sheffield Teaching Hospitals NHS FT
Duration of Study in the UK
3 years, 0 months, 1 days
Background: Parkinson’s Disease (PD) is relentlessly progressive and incurable. There is growing evidence for mitochondrial dysfunction in PD. Rescue of mitochondrial function is therefore a promising therapeutic target for future disease-modifying therapy which would slow down the disease progression.
Pilot data: We previously demonstrated marked impairment of mitochondrial function in fibroblasts of PD patients with the two most common forms of genetically defined familial PD (namely due to parkin or LRRK2 mutations). Our more recent work also confirms mitochondrial dysfunction in skin fibroblasts from a subset of patients with the much more common sporadic form of PD. However, it is unclear whether the mitochondrial dysfunction observed in the peripheral tissue correlates with mitochondrial function in the brain. Modern imaging techniques, in particular 31P-Magnetic Resonance Spectroscopy (31P-MRS), allow the indirect quantification of ATP levels in patients’ brains.
Hypothesis: Mitochondrial dysfunction in the peripheral tissue (skin fibroblasts) of patients with PD correlates with mitochondrial dysfunction in their brain tissue as quantified with 31P-MRS. The extent of the mitochondrial dysfunction will correlate with the predicted disease progression.
Aims and objectives: We will recruit 50 research participants (35 patients with PD and 15 controls) and undertake the following in all research participants: 1. Detailed clinical assessment (patients only), 2. Skin biopsies to obtain fibroblasts and assess mitochondrial function (e.g. quantification of intracellular ATP levels), 3. 31P-Magnetic Resonance Spectroscopy (31P-MRS), 4. Correlation analysis.
Expected outcome and benefit to patients: Confirmation of a correlation between central and peripheral mitochondrial dysfunction would be of considerable importance for the development of personalized medicine and disease-stratification in PD. A correlation of the predicted disease severity with the extent of the mitochondrial dysfunction would also be of considerable value to identify those PD patients who are most at need of disease-modifying therapy which would slow down disease progression.
North West - Liverpool Central Research Ethics Committee
Date of REC Opinion
6 Jun 2018
Further Information Favourable Opinion