October 2017 | Issue 32
Scientists add hope of new treatment to Parkinson’s disease armamentarium


By Nicole Lim, Senior Assistant Director, Communications & External Relations

Most of us take drinking a cup of coffee without spilling the contents for granted. Not so for actor Michael J Fox, who shared in an interview earlier this year that when he tries to make his wife Tracey a cup of coffee, he’d spill most of it while carrying it over.

These involuntary tremors and stiffness are hallmarks of Parkinson’s disease, a progressive neurodegenerative condition caused by low levels of dopamine in the brain. Scientists have long assumed that these symptoms manifest because low dopamine levels more severely suppress action instructions sent from the part of the brain that controls movement, called the basal ganglia. Many treatments have, therefore, focused on ‘topping up’ dopamine levels in the brain to restore the number of action instructions sent.

In a scientific breakthrough, scientists from LKCMedicine and the Korean Advanced Institute of Science & Technology (KAIST) have overturned three decades of conventional wisdom in Parkinson’s disease research, opening up potential new avenues of treatment that could help alleviate the motor problems experienced by the estimated more than 10 million people living with the condition worldwide.

Using optogenetics, a light-based experimental technique, the research team, which was led by KAIST Professor Daesoo Kim and LKCMedicine Professor of Neuroscience & Mental Health George Augustine, tested this assumption in mice.

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Prof George Augustine together with KAIST have made a scientific breakthrough that could change the way scientists approach Parkinson's disease

They found that when action instructions from the basal ganglia to the thalamus, the brain’s central processing hub, were more strongly suppressed, the motor controlling part of the brain actually became hyperactive.

This hyperactivity, rather than a lack of activity, leads to the abnormal muscular stiffness and tremors associated with Parkinson’s disease. The key is a neural phenomenon that kicks in after such strong suppression, known as rebound firing.

Prof Augustine said, “Rebound firing is a form of compensation built into the nerve cells of the thalamus. As suppression of nerve cell activity stops, there is a temporary increase in activity that counter-balances the suppression. We were surprised to see the very important role that such rebound firing plays in controlling movement, both in normal conditions and to an extreme degree in Parkinson’s disease.”

Conversely, when rebound firing was itself blocked in mice that were genetically engineered to be dopamine deficient, they showed normal movement without Parkinson’s disease-like symptoms, proving the key role of rebound firing.

Prof Kim said, “This study overturns three decades of consensus on the provenance of Parkinsonian symptoms.”

Prof Augustine added, “Our findings are a breakthrough, both for understanding how the brain normally controls the movement of our body and how this control goes awry during Parkinson’s disease and related dopamine-deficiency disorders.”

Lead author of the paper published in Neuron on 30 August, Dr Jeongjin Kim, who now works at the Korea Institute of Science and Technology (KIST), said, “The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a pre-cursor to dopamine.”

The study took five years to complete, and includes researchers from the Department of Bio & Brain Engineering at KAIST.

The research team will move forward by investigating how hyperactivity in neurons in the thalamus leads to abnormal movement, as well as developing therapeutic strategies for the disease by targeting this neural mechanism, thereby restoring control over their movements to people living with Parkinson’s disease.