Study supports fast-track to clinical trials for new Parkinson’s treatment

Posted on Monday 10 August 2015

The research, which involved scientists in the Department of Biology at York and the University of Sheffield’s Institute for Translational Neuroscience, supports the fast-tracking of the drug ursodeoxycholic acid (UDCA for a clinical trial in Parkinson’s patients.

The research is the first to demonstrate beneficial effects of UDCA on dopaminergic neurons, the nerve cells affected in Parkinson’s disease, in a genetic animal model of Parkinson’s disease. The research published in Neurology is funded by Parkinson’s UK, the Wellcome Trust and the Norwegian Parkinson Foundation,

A mutation in the LRRK2 gene is the single most common inherited cause of Parkinson’s disease. However, the precise mechanism that leads to Parkinson’s is still unclear.

Defects in mitochondria, and as a consequence reduced energy levels, are a factor in a number of diseases that affect the nervous system including Parkinson’s and Motor Neuron Disease. Nerve cells have a particularly high energy demands, therefore defects in the cell’s energy generators will crucially affect their survival.

The York researchers, Rebecca Furmston and Dr Chris Elliott, demonstrated the beneficial effects of UDCA in vivo using the fruit fly (Drosophila melanogaster). In fruit flies, the mitochondrial defects caused by the LRRK2 mutation to dopaminergic neurons can be monitored through the progressive loss of visual function.  Flies carrying the mutation maintained their visual response when fed with UDCA.

Dr Elliott said: “The treatment of fruit flies carrying the faulty LRRK2 gene with UDCA showed a profound rescue of dopaminergic signalling. Feeding the flies with UDCA partway through their life slows the rate at which the fly brain then degenerates. Thus, mitochondrial rescue agents may be a promising novel strategy for disease-modifying therapy in LRRK2-related Parkinson’s.”

Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield and Honorary Consultant Neurologist at the Sheffield Teaching Hospitals NHS Foundation Trust, said: “Following on from the promising results of our in vitro drug screen, we were keen to further investigate and confirm the potential of UDCA in vivo. UDCA has been in clinical use for decades and thus could be advanced to the clinic rapidly if it proves beneficial in clinical trials.”

Professor Bandmann added: “Whilst we have been looking at Parkinson’s patients who carry the LRRK2 mutation, mitochondrial defects are also present in other inherited and sporadic forms of Parkinson’s, where we do not know the causes yet. Our hope is therefore, that UDCA might be beneficial for other types of Parkinson’s disease and might also show benefits in other neurodegenerative diseases .“

Dr Arthur Roach, Director of Research and Development at Parkinson’s UK, which part-funded the study, said: “There is a tremendous need for new treatments that can slow or stop Parkinson’s.  Because of this urgency, the testing of drugs like UCDA, which are already approved for other uses, is extremely valuable. It can save years, and hundreds of millions of pounds. 

“It’s particularly encouraging in this study that even at relatively low concentrations the liver drug still had an effect on Parkinson’s cells grown in the lab. This type of cutting-edge research is the best hope of finding better treatments for people with Parkinson’s in years, not decades.”