Two Antimalarials May Benefit Parkinson’s Disease Patients

Authors of recent study have reported that chloroquine and amodiaquine, two antimalarial drugs, can potentially be used for the treatment of Parkinson’s disease (PD).  

Senior author Kwang-Soo Kim, of the McLean Hospital and Program in Neuroscience at Harvard Medical School in Belmont, Massachusetts, and colleagues identified three nuclear receptor related 1 protein (Nurr1) agonists from a U.S. Food and Drug Administration–approved drug library (amodiaquine, chloroquine, and the pain reliever glafenine) that share an identical chemical scaffold (4-amino-7-chloroquinoline).

Glafenine demonstrated a weaker activity, and thus researchers focused on amodiaquine and chloroquine for the analysis.

The authors reported that the antimalarial drugs directly binded to Nurr1, thus activing Nurr1 function, and ameliorated the behavioral defects of PD in rats.

“Our research showed the possibility that Nurr1 is a valid target and that Nurr1 agonists may provide the neuroprotective therapeutics for PD,” Dr. Kim said. “This means that these new drugs may slow down the disease progress. At present, there are no such treatments or drugs.”

PD is a common disease of the central nervous system in which patients experience muscle rigidity; hand, arm, leg, jaw, and face tremors; and speech and gait changes. It is caused mainly by the degeneration of midbrain dopamine (mDA) neurons. Treatment is focused on symptom improvement.

“At present, all available treatments are only symptomatic and cannot slow down the disease process,” said Dr. Kim. “Our studies suggest that these Nurr1 agonists may provide a neuroprotective therapy for PD. In particular, all three hit compounds we found have an identical chemical scaffold, indicating that we can make better drugs by chemical modifications.”

Nurr1 is important for the development and maintenance of mDA neurons, and it has been identified as a potential target for treating PD.

“However, nobody could identify a small molecule that can activate Nurr1’s function by direct binding to Nurr1,” Dr. Kim pointed out. “In our study, we found that all three hit compounds directly bind to the ligand binding domain (a part of Nurr1 protein) and then activate its function.”

This study was published in the Proceedings of the National Academy of Sciences of the United States of America.

-Meredith Edwards White

Reference:

1. Kim CH, Han BS, Moon J, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease. Proc Natl Acad Sci USA. 2015;112(28):8756-8761.