Niclosamide, an oral medication widely used to eradicate tapeworm infections, may have the potential to slow disease progression in Parkinson’s patients with mutations in the PINK1 gene, researchers report.
Their study, “The Anthelmintic Drug Niclosamide and its Analogues Activate the Parkinson’s Disease Associated Protein Kinase PINK1,” was published in the journal ChemBioChem.
Strong evidence suggests mutations in the PINK1 gene are linked to early onset hereditary Parkinson’s. When mutated, tangles of the PINK1 protein build inside mitochondria — the cell’s powerhouse — within brain cells and damage them. (Most Parkinson’s cases are sporadic, however; only about 10% of all cases are in people with a family history of this disease. PINK1 mutations are linked to autosomal recessive disease inheritance, in which both copies of a gene are mutated.)
Treatments targeting that protein to improve how it works in this group of patients, however, remain to be discovered.
Niclosamide is an established and safe treatment for tapeworm, and previous research has shown it has a positive impact on mitochondria in cells.
With this in mind, researchers at Cardiff University and University of Dundee prepared lab-grown cells that expressed Parkin, a causative gene of Parkinson’s. They prepared two batches of cells: wild-type, or normal, cells, and cells that did not express the PINK1 protein.
They then treated the cells with different concentrations of niclosamide. Results showed that niclosamide and a niclosamide-like compound, called AM85, activated PINK1 in the cells.
The researchers next investigated, using the same procedure, if the treatment migth also work in brain cells (the study was not clear as to whether human or animal brain cells were used). Results showed it did, the researchers said, noting that this was also the first report of PINK1 activation being detected in brain cells.
“Our findings suggest that niclosamide and its analogues are robust compounds to study the PINK1 pathway and may hold promise as a therapeutic strategy in Parkinson’s and related disorders,” they wrote.
Because PINK1 activation has the potential to stop neurodegeneration, treatments that can promote this may benefit certain patients with Parkinson’s or related disorders. The researchers are planning further studies.
“This work represents the first report of a clinically used drug to activate PINK1 and may hold promise in treating Parkinson’s disease,” Youcef Mehellou, with the School of Pharmacy and Pharmaceutical Sciences at Cardiff and a study co-leader, said in a news release. “We will now take our findings to the next level by evaluating the ability of niclosamide to treat Parkinson’s disease in disease models.”