Pioneering research led by academics at the Sheffield Institute of Translational Neuroscience (SITraN), in collaboration with scientists at the University of York, is supporting a rapid investigation of the drug ursodeoxycholic acid (UDCA) for a clinical trial in patients with Parkinson's. Dr. Heather Mortiboys, Parkinson's UK Senior Research associate at the University of Sheffield, stated, "We demonstrated the beneficial effects of UDCA in the tissue of LRRK2 carriers with Parkinson's disease and in the tissue in asymptomatic LRRK2 carriers. In both cases, UDCA improved mitochondrial function as demonstrated, through the increase in oxygen consumption and an increase in cellular energy levels. " Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield and Honorary Consultant Neurologist at Sheffield Teaching Hospitals, added: "While we looked at Parkinson's patients carrying the LRRK2 mutation, mitochondrial defects were also present in other (hereditary) forms of Parkinson's, the causes of which we do not yet know. Our hope, therefore, is that UDCA could be beneficial for other forms of Parkinson's disease and perhaps provide benefits in other neurodegenerative diseases. " The study is the first to demonstrate the beneficial effects of UDCA on dopaminergic neurons (the nerve cells affected by Parkinson's disease) in a flight model of Parkinson's disease, which has the same genetic alteration 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's Foundation. A mutation in the LRRK2 gene is the most common cause of Parkinson's disease. However, the exact cause that leads to Parkinson's is still unclear. Defects in mitochondria, and as a result reduced energy levels, is often a major factor in diseases affecting the nervous system. Examples include Parkinson's disease and Motor Neuron Disease. Nerve cells have particularly high energy requirements. Therefore, defects in the cell's energy generators will be crucial to their survival. Professor Bandmann added, "As a result of the promising results of our reaction tube tests (in vivo), we were excited to further investigate and confirm the potential of UDCA in vivo, and in a living organism. "UDCA has been in clinical use for decades and can therefore be quickly brought to the clinic if it proves beneficial in clinical trials." Collaborators Rebecca Furmston (White Rose student to PhD) and Dr. Chris Elliott, of York University's Department of Biology, demonstrated the beneficial effects of UDCA in vivo using the fruit fly (Drosophila melanogaster). In fruit flies, mitochondrial defects caused by the mutation of LRRK2 to dopaminergic neurons can be controlled by the progressive loss of visual function. Flies carrying the mutation retain their visual response when fed UDCA. Dr. Elliott said, "Treatment of fruit flies carrying the defective LRRK2 gene with UDCA showed a profound rescue of dopaminergic signaling. Feeding the flies with UDCA halfway through their lives shows the rate at which the fly brain then degenerates. Therefore, mitochondrial rescue may be a promising new strategy for disease alleviating therapy in LRRK2-related Parkinson's. " Dr Arthur Roach, director of research and development at Parkinson's UK who funded the study, said, "There is a huge need for new treatments that slow or stop Parkinson's. "Because of this urgency, testing drugs like UCDA, which is already approved for other uses, is very valuable. It can save years but also hundreds of millions of dollars. "It is particularly encouraging in this study that even at relatively low concentrations, the liver drug still affects Parkinson's cells created in the laboratory. "This kind of cutting-edge research is the best hope for finding better treatments for people with Parkinson's. Because of this, this can be done in years, not decades." Source: Click here

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