The researchers say their study shows the potential for using existing drugs to protect the brain against the progress of Parkinson’s disease.
The international team behind the study – including members from Nanyang Technological University (NTU) in Singapore and McLean Hospital and Harvard Medical School in Belmont, MA – reports the findings in the Proceedings of the National Academy of Sciences.
An estimated 10 million people worldwide are living with Parkinson’s disease – a progressive, neurological disorder that mostly strikes after middle age. As the disease unfolds, people gradually lose their ability to control their movements and find it increasingly difficult to walk, talk and look after themselves.
Parkinson’s disease disrupts the brain cells that release dopamine – a chemical that is important for control of movement. The cells gradually deteriorate and die.
Current methods for treating Parkinson’s disease aim to make up for the loss of dopamine through drugs or surgically with deep brain stimulation. However, as senior author Kwang-Soo Kim, a professor in psychiatry and neuroscience at McLean Hospital, and a leading expert in Parkinson’s disease, explains:
“These pharmacological and surgical treatments address the patient’s symptoms, such as to improve mobility functions in the early stages of the disease, but the treatments cannot slow down or stop the disease process.”
For their study, Prof. Kim and colleagues focused on the role of the receptor Nurr1, a brain protein that is thought to protect dopamine cells in two ways: it is important for their development and maintenance and it also protects them from inflammation-induced death.
Two FDA-approved antimalaria drugs target Nurr1
Previous studies have suggested Nurr1 as a potential target for treating Parkinson’s disease, but until this study, nobody had found a molecule that could bind to it.
The team screened around 1,000 drugs already approved by the Food and Drug Administration (FDA) and found two antimalaria drugs – chloroquine and amodiaquine – that boost both protective effects of Nurr1.
When they tested the two drugs in rats with Parkinson’s-like symptoms, their movement control appeared to improve and they did not show detectable signs of dyskinesia – a side effect often seen with current Parkinson’s drugs.
The researchers conclude that their study offers “proof of principle” that small molecules that target Nurr1 can be used to protect the brain against the progress of Parkinson’s disease.
Co-author Ho Sup Yoon, an associate professor of structural biology and biochemistry at NTU, and an expert in drug discovery and design, adds:
“Our research also shows that existing drugs can be repurposed to treat other diseases and once several potential drugs are found, we can redesign them to be more effective in combating their targeted diseases while reducing the side effects.”
The team is already looking for other drugs that may halt or reverse the progress of Parkinson’s disease, and they plan to improve the drug design and carry out clinical trials of chloroquine and amodiaquine for treating Parkinson’s disease.
Meanwhile, progress in discovering potential treatments for Parkinson’s is also being made elsewhere. For example, in February 2015, Medical News Today learned about a study led by the University of Bath in the UK that found a peptide may slow progression of Parkinson’s disease. The study showed how the peptide – a chain of amino acids – sticks to a faulty cell protein and stops it stacking into toxic fibrils that kill off dopamine cells.
Written by Catharine Paddock PhD