Scientists from the United Kingdom and Norway have demonstrated that ursodeoxycholic acid (UDCA), a drug already approved for liver disease in humans, could be a viable candidate for the treatment of Parkinson’s disease.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that results from the depletion of the neurotransmitter dopamine in the brain. About 7-10 million individuals are afflicted with this condition worldwide. PD is the second most common neurodegenerative disorder after Alzheimer’s disease.

The symptoms of PD occur as a result of the death of neurons (brain cells) in localized brain structures, called the substantia nigra and locus coeruleus. These neurons normally produce dopamine, a neurotransmitter that acts as a chemical signal to brain regions responsible for motor activity.

It has been reported that nerve cells require high energy levels, which are provided by the powerhouses of cells, called mitochondria. Mitochondrial defects have been reported in neurodegenerative disorders, including PD. The following are the major findings from the study being discussed here:

• There were significant benefits to dopaminergic neurons upon treatment with UDCA in both non-manifesting PD patients’ tissue as well as tissue from patients with mutant leucine-rich repeat kinase 2 (LRRK2) gene, which is considered the greatest genetic contributor to PD.
  
• Using a transgenic fly model of PD, it has been demonstrated for the first time that the function of neurons improved with the use of UDCA. In fruit flies, mitochondrial malfunction owing to defective LRRK2 is manifested as gradual loss of vision. UDCA was successful in rescuing the loss of visual function in fruit fly model of PD.

The lead author of the study, Dr. Heather Mortiboys, has said in the News Release, “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.”

The senior author of the study, Dr. Bandmann says in the News Release, “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.”

Since UDCA is already approved for human use, clinical trials could be carried out without much delay. If found effective in the trials, UDCA could potentially be available as a treatment option for PD very soon. This could save millions of dollars in research and more importantly, valuable time. The study also brings hope to the millions of individuals who are suffering from, or likely to get diagnosed with, PD.

Written by Mangala Sarkar Ph.D.

Primary References

Mortiboys, H., Furmston, R., Bronstad, G., Aasly, J., Elliott, C., & Bandmann, O. (2015). UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo. Neurology. (n.d.). Retrieved August 10, 2015, from http://www.neurology.org/content/early/2015/08/07/WNL.0000000000001905

Promising drug for Parkinson’s disease: Study supports fast track to clinical trials. (n.d.). Retrieved August 10, 2015, from http://www.alphagalileo.org/ViewItem.aspx?ItemId=155308&CultureCode=en

DoveMed Resource

Parkinson's Disease (PD). (n.d.). Retrieved August 13, 2015, from http://www.dovemed.com/parkinsons-disease-pd/

Additional References

Statistics on Parkinson's. (n.d.). Retrieved August 13, 2015, from http://www.pdf.org/en/parkinson_statistics

Bolam, J., & Pissadaki, E. (2012). Living on the edge with too many mouths to feed: Why dopamine neurons die. Movement Disorders, 27(12), 1478-1483.

LRRK2 and Parkinson's Disease | Parkinson's Disease Information. (n.d.). Retrieved August 13, 2015, from https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?lrrk2