Liver disease drug could slow Parkinson's disease

Ursodeoxycholic acid has been used to treat liver disease for decades and as
such is already approved for clinical use.

August 10,2015

Researchers have discovered a drug that has long been used to treat liver disease could also be used to slow down the effects of Parkinson's disease.Ursodeoxycholic acid (UDCA) had beneficial effects on fruit fly nerve cells with mutations in the LRRK2 gene - the most common inherited cause of Parkinson's disease.

The study was conducted by researchers from the Sheffield Institute of Translational Neuroscience (SITraN) and the University of York - both in the UK. Their work is published in Neurology.

"We demonstrated the beneficial effects of UDCA in the tissue of LRRK2 carriers with Parkinson's disease as well as currently asymptomatic LRRK2 carriers," states study author Dr. Heather Mortiboys of SITraN. "In both cases, UDCA improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels."Mitochondria give cells the energy they need to carry out their jobs. Defects in mitochondria such as those caused by the LRRK2 gene mutation lead to reduced energy levels that can contribute toward the development of several diseases affecting the nervous system. These include motor neuron disease and Parkinson's disease.

According to the National Institute of Neurological Disorders and Stroke (NINDS), at least 500,000 people are estimated to have Parkinson's disease in the US. The disorder is characterized by shaking limbs, particularly when the body is at rest, along with slow movement. Symptoms typically get worse over time. 

Approved drug could save years of research

Dr. Oliver Bandmann, professor of movement disorders neurology at the University of Sheffield, explains the wider implications for their research:

"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."

In fruit flies, the effects of LRRK2 gene mutation on mitochondria can be tracked through the loss of visual function. The researchers fed flies carrying the LRRK2 mutation with UDCA partway through their lives and found that the drug managed to preserve their visual response.

Dr. Chris Elliott, from the University of York, explains that the UDCA treatment demonstrated a marked rescue effect on neural signaling:

"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."

Dr. Bandmann states that because UDCA has been in clinical use for decades, it could be brought forward to treat Parkinson's disease quickly if it proves beneficial in clinical trials. As the drug is already approved to treat other conditions, its use could save significant amounts of time and money in research.

The study was partly funded by Parkinson's UK- a charity for supporting people with the neurological condition. The charity's director of research and development, Dr. Arthur Roach, describes the findings as "particularly encouraging," and that the need for new treatments for the disease is urgent.

"This type of cutting edge research is the best hope of finding better treatments for people with Parkinson's in years, not decades," he says.

Last month, Medical News Today reported on a breakthrough study that identified two existing antimalarial drugsthat showed promise in protecting the brain against the progression of Parkinson's disease.

Written by James McIntosh

http://www.medicalnewstoday.com/articles/297941.php?tw

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Promising drug for Parkinson's disease: Study supports fast track to clinical trials

A drug which has already been in use for decades to treat liver disease could be an effective treatment to slow down progression of Parkinson's disease, scientists from the University of Sheffield have discovered.

• Marked rescue effect of the drug UDCA on cell batteries (mitochondria) in Parkinson's disease patient tissue
• First study to demonstrate beneficial effects of UDCA on the nerve cells affected in Parkinson's disease in a genetic animal model of Parkinson's disease
• UDCA is already approved for use in human liver disease
• Results of the study support fast track of UDCA to clinical trials and could save years of research and hundreds of millions of pounds 

The pioneering research led by academics from the Sheffield Institute of Translational Neuroscience (SITraN), in collaboration with scientists from the University of York, supports the fast-tracking of the drug ursodeoxycholic acid (UDCA) for a clinical trial in Parkinson's patients.

Dr Heather Mortiboys, Parkinson's UK Senior Research Fellow from the University of Sheffield, explained: "We demonstrated the beneficial effects of UDCA in the tissue of LRRK2 carriers with Parkinson's disease as well as currently asymptomatic LRRK2 carriers. In both cases, UDCA improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels."

Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield and Honorary Consultant Neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, 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."

The research is also the first to demonstrate beneficial effects of UDCA on dopaminergic neurons, the nerve cells affected in Parkinson's disease, in a fly model of Parkinson's disease which carries the same genetic change as some patients with the condition.

The study published in the journal 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.

Professor Bandmann added: "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 - in a living organism.

"UDCA has been in clinical use for decades and thus could be advanced to the clinic rapidly if it proves beneficial in clinical trials."

Collaborators Rebecca Furmston, White Rose PhD student, and Dr Chris Elliott, from the University of York's Department of Biology, 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."

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." 

Parkinson's UK

Every hour, someone in the UK is told they have Parkinson's. It affects 127,000 people in the UK - which is around one in 500 of the population. Parkinson's is a degenerative neurological condition, for which there currently is no cure. The main symptoms of the condition are tremor, slowness of movement and rigidity. Parkinson's UK is the UK's leading charity supporting those with the condition. Its mission is to find a cure and improve life for everyone affected by Parkinson's through cutting edge research, information, support and campaigning.

http://www.medicalnewstoday.com/releases/297936.php?tw