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Scientists Design a Potential Drug Compound that Attacks Parkinson’s Disease on Two Fronts

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have found a compound that could counter Parkinson’s disease in two ways at once.

In a new study published recently online ahead of print by the journal ACS Chemical Biology, the scientists describe a “dual inhibitor”—two compounds in a single molecule—that attacks a pair of proteins closely associated with development of Parkinson’s disease.

“In general, these two enzymes amplify the effect of each other,” said team leader Phil LoGrasso, a TSRI professor who has been a pioneer in the development of JNK inhibitors for the treatment of neurodegenerative diseases. “What we were looking for is a high-affinity, high-selectivity treatment that is additive or synergistic in its effect—a one-two punch.”

That could be what they found.

This is a brain scan of a person with Parkinson's disease.

Researchers describe a “dual inhibitor” which attacks a pair of proteins associated with the development of Parkinson’s disease. The image is a brain scan of a Parkinson’s disease patient.

This new dual inhibitor attacks two enzymes—the leucine-rich repeat kinase 2 (LRRK2) and the c-jun-N-terminal kinase (JNK)—pronounced “junk.” Genetic testing of several thousand Parkinson’s patients has shown that mutations in the LRRK2 gene increase the risk of Parkinson’s disease, while JNK has been shown to play an important role in neuron (nerve cell) survival in a range of neurodegenerative diseases. As such, they have become highly viable targets for drugs to treat disorders such as Parkinson’s disease.

A dual inhibitor ultimately would be preferred over separate individual JNK and LRRK2 inhibitors because a combination molecule would eliminate complications of drug-drug interactions and the need to optimize individual inhibitor doses for efficacy, the study noted.

Now the team’s new dual inhibitor will need to be optimized for potency, high selectivity (which reduces off-target side effects) and bioavailability so it can be tested in animal models of Parkinson’s disease.

Notes about this neurology and Parkinson’s disease research

The first author of the study, “A Small Molecule Bidentate-Binding Dual Inhibitor Probe of the LRRK2 and JNK Kinases,” is Yangbo Feng of TSRI. Other authors include Jeremy W. Chambers, Sarah Iqbal, Marcel Koenig, HaJeung Park, Lisa Cherry, Pamela Hernandez and Mariana Figuera-Losada. For more information see

The study was supported by the National Institutes of Health grant NS057153.

Contact: Office of Communication – Scripps Research Institute
Source: Scripps Research Institute press release
Image Source: The Parkinson’s brain scan image is credited to NIBIB/NIH and is in the public domain.
Original Research: Abstract for “A Small Molecule Bidentate-Binding Dual Inhibitor Probe of the LRRK2 and JNK Kinases” by Yangbo Feng, Jeremy W. Chambers, Sarah Iqbal, Marcel Koenig, HaJeung Park, Lisa Cherry, Pamela Hernandez, Mariana Figuera-Losada, and Philip V. LoGrasso in ACS Chemical Biology. Published online June 10 2013 DOI: 10.1021/cb3006165

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