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Compound in Fruit and Perfume Could Be Used To Treat Parkinson's Disease

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A study by researchers at Johns Hopkins Medicine suggests that a compound found naturally in herbs and fruit might show potential as a treatment for Parkinson's disease. The work is published in Science Translational Medicine.

A need for new drugs to treat Parkinson's disease

A cure for the progressive neurodegenerative disorder Parkinson's disease is yet to be discovered. Consequently, therapeutics currently prescribed for patients are symptomatic only; they aim to alleviate the
symptoms of the condition, which can include tremor, bradykinesia (slowed movement) rigid muscles and speech changes. These medications cannot target the root cause of Parkinson's disease – neuronal death in a brain region known as the substantia nigra.

The discovery of novel therapeutics is therefore an important goal for this area of research. Now, scientists at the Johns Hopkins Medicine have contributed to a growing body of work that suggests farnesol may be a compound of interest for treating Parkinson's disease.

Screening existing drug libraries

"We initially sought to identify PARIS inhibitors as new treatments for Parkinson's disease,"
Professor Ted Dawson, director of the Institute for Cell Engineering at Johns Hopkins Medicine told Technology Networks.

PARIS is an acronym for the protein parkin-interacting substrate, which accumulates in the brain of Parkinson's disease patients and reduces the production of a second protein – PGC-1alpha – that shields neurons from reactive oxygen molecules. A reduction in PGC-1alpha levels ultimately leads to the death of dopamine neurons. "We and others have shown in multiple models of Parkinson's disease that PARIS plays a central role in pathophysiology by inhibiting PGC-1 alpha, a key regulator of mitochondrial health," explained Dawson.

From perfume to Parkinson's disease

Dawson and colleagues screened over 230,000 drug-like molecules known to inhibit the PARIS protein. "In a non-biased screen, farnesol rose to the top of the compounds in our library that inhibited PARIS," he said.

What is farnesol?

Farnesol is a naturally occurring compound that can be found in fruits and vegetables, such as tomatoes and peaches, and in herbs. It is often also used as a component in perfumes, offering a sweet floral scent.]

Dawson and team utilized cell and animal models of Parkinson's disease to explore the inhibiting powers of farnesol against the protein PARIS. "We used several mouse models in our study and showed that farnesol protects against the loss of dopamine neurons in a genetic model of autosomal recessive Parkinson's disease due to parkin loss, and farnesol protects against the loss of dopamine neurons in the alpha-synuclein preformed model of sporadic Parkinson's disease," Dawson said. As the compound was protective in both animal models of the disease, the researchers predict that it is likely to have a "high probability" of success in humans. "We think farnesol is an exciting therapeutic opportunity for treatment of Parkinson's disease," Dawson added.

Moving farnesol to human clinical trials

Farnesol is not approved by regulatory bodies for medicinal use, and it can be challenging to progress a naturally occurring compound through approval processes. "The same regulatory and Food and Drug Administration approval process is required for a natural compound. In some ways, natural compounds are disadvantageous, because it is often difficult to patent a natural compound," Dawson explained.

Nonetheless, the researchers are currently in the process of moving farnesol forward for a clinical trial in humans. In parallel, they continue to screen for other compounds that are capable of inhibiting the PARIS protein.

Professor Ted Dawson was speaking to Molly Campbell, Science Writer for Technology Networks.

Areum J, Yunjong L, Tae-In K et al. PARIS farnesylation prevents neurodegeneration in models of Parkinson’s disease. Sci Trans Med. 2021; 13 (604): eaax8891. doi: 10.1126/scitranslmed.aax8891.