Sheffield Institute for
Translational Neuroscience

Parkinson's disease

Parkinson’s disease is a progressive neurological condition and the second most common neurodegenerative disease. Each day, 80 people in the UK are newly diagnosed with the disease which affects over six million people globally. Parkinson’s is not only a movement disorder but often causes non-motor problems such as depression or dementia as well. There is currently no cure or disease-modifying therapy.

The pioneering Parkinson’s research, led by Professor Oliver Bandmann at SITraN, has succeeded in establishing new disease models, uncovering disease mechanisms, identifying drug targets and promising candidates for a neuroprotective therapy to slow down or stop Parkinson’s disease.

Zebrafish as a new vertebrate animal model for
Parkinson’s disease

The SITraN team was the first group worldwide to establish a zebrafish model of familial Parkinson’s disease. They demonstrated that Parkin-deficient zebrafish share key features with human parkin-mutant Parkinson’s disease patients, namely mitochondrial dysfunction and loss of dopamine-producing nerve cells. Most recently, the group has identified a novel dysregulated pathway in PINK1 mutant zebrafish. The team has discovered that inhibiting a protein called Tigar normalises mitochondrial function and rescues the dopaminergic neurons. Tigar is therefore a promising novel therapeutic target for disease modification in Parkinson’s disease.

Detailed characterisation of mitochondrial dysfunction and identification of neuroprotective compounds as candidates for disease-modifying treatment

The group was the first worldwide to assess in detail defects in mitochondrial function and morphology in skin cells derived from patients with familial Parkinson’s caused by the LRRK2G2019S or parkin mutations. They subsequently undertook the first screen for neuroprotective compounds in human Parkinson’s tissue.

2,000 drugs were assessed for their rescue effect on mitochondrial function. Several promising compounds were identified, including the drug ursodeoxycholic acid (UDCA). This FDA-licensed drug is very well tolerated and has been in clinical use for several decades to treat certain forms of liver disease. A funding application has been made for a multi-centre study to confirm not only the drug’s safety and tolerability in people with Parkinson’s disease but also to test UDCA against placebo for its effectiveness in slowing down Parkinson’s progression.

Tracking Parkinson’s and risk factors in Parkinson’s disease

Professor Bandmann’s team is participating in the world’s largest long-term study on Parkinson’s disease called Tracking Parkinson’s. Across the UK, 3,000 patients are being recruited into this study which is funded by the charity Parkinson’s UK. They are also investigating risk factors for the disease such as the role of REM sleep Behaviour Disorder (RBD) in a collaboration with Dr Michele Hu from Oxford University (Monument Discovery Award).

Mitochondrial biomarkers in Parkinson’s disease

The team is currently undertaking a detailed assessment of mitochondrial function and morphology in patients with sporadic Parkinson’s disease to identify patients most likely to benefit from mitochondrial rescue drugs. The role of microRNAs in developmental regulation and the pathogenesis of Parkinson’s is also being investigated, as well as the potential to use microRNAs as disease biomarkers for early diagnosis and disease monitoring.

ZFv.png