This preclinical study aims to gather evidence on whether two compounds – probucol and chlorogenic acid – have a neuroprotective effect in models of Parkinson’s.
About the study
Both probucol and chlorogenic acid have been evaluated by the International Linked Clinical Trials (iLCT) committee, in 2023 and 2021 respectively. However, they were lacking some key evidence to recommend them moving into clinical trial. Dr Poonam Thakur, from the Indian Institute of Science Education and Research (IISER) in Thiruvananthapuram, is the recipient of our second annual iLCT Pipeline Project grant – our funding programme which commissions research based on recommendations by the iLCT committee.
Dr Thakur’s team will be observing the effects of probucol and chlorogenic acid in a model of Parkinson’s to determine (1) how easily these compounds are able to access the brain; (2) whether the compounds exert a protective effect on the dopamine nerve cells (neurons) lost in Parkinson’s; (3) if the compounds affect other processes associated with Parkinson’s progression, such as inflammation; and (4) if there are any differences in responses between sexes. We hope the results of this study will provide the necessary evidence to determine if and how these drugs should be studied further in Parkinson’s.
Study overview
- Researcher: Dr Poonam Thakur
- Institution: Indian Institute of Science Education and Research (IISER) Thiruvananthapuram
- Project Type: Preclinical
- Status: Active
- Start Date: April 2024
- iLCT-evaluated: Probucol (2023) & chlorogenic acid (2021)
- Therapy Targets: Neuroprotection
More about the study
What are the compounds being tested?
Probucol is currently used to treat high cholesterol; however, evidence suggests it may also be anti-inflammatory and have a protective effect on nerve cells (neurons). Neuroinflammation, or inflammation in the brain, is considered a driver for neuron loss in Parkinson’s; therefore, if probucol can reduce inflammation, it may be able to slow progression. A recent screening study has also identified probucol as a potential mitigator of mitochondrial dysfunction. Mitochondria, the part of the cell responsible for energy production, are also known to be dysfunctional in Parkinson’s, driving progression of the condition.
Learn more about neuroinflammation and mitochondrial dysfunction.
Chlorogenic acid is a compound found naturally in coffee as well as other foods. Evidence suggests chlorogenic acid may reduce the build-up of the protein alpha-synuclein in preclinical models of Parkinson’s. Dysfunctional copies of alpha-synuclein build-up and form clumps called Lewy bodies in the dopamine neurons of people with Parkinson’s. If not disposed of, these clumps interfere with cellular processes and may eventually lead to cell death. Alpha-synuclein accumulation is a hallmark of Parkinson’s and considered to be a major driver of progression. The mechanism for how chlorogenic acid may mitigate this is not well understood; however, researchers believe it may boost the cell recycling process (autophagy), therefore increasing the rate of alpha-synuclein breakdown.
Learn more about alpha-synuclein.
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