Pushing the frontiers of neuroscience with pioneering stem cell therapies

Pushing the frontiers of neuroscience with pioneering stem cell therapies
By Dr Chua Li Min, Science writer

Prof Zhang Suchun (left) joined by his team in the lab // Credit: Norfaezah Abdullah, Duke-NUS

At the forefront of neurological innovation, the newly established GK Goh Centre for Neuroscience at Duke-NUS has achieved a global first. The team has successfully cultivated a specific type of stem cell-derived neuron known as norepinephrine neurons, an accomplishment unmatched anywhere in the world.

“With these functional brain cells, we can study how they age and uncover their roles in neurodegenerative conditions. The new insights will help in finding new and more effective therapies to treat brain diseases and perhaps even slow down the ageing process,” explained centre director Professor Zhang Suchun, who is also director of Duke-NUS’ Neuroscience & Behavioural Disorders Programme.

Norepinephrine neurons are specialised nerve cells located in the brainstem, which connect with every part of the brain and spinal cord.

These specific neurons degenerate in many conditions such as Alzheimer’s disease and Parkinson’s disease—often as early as ten years before a patient shows any symptoms of the disease.

“Professor Zhang and his team have also collected a comprehensive spectrum of biological samples for unravelling the mysteries of brain ageing and developing new therapies for otherwise incurable brain conditions. We are immensely grateful to the GK Goh family for their support in this ground-breaking endeavour.”
Prof Thomas Coffman

With typically only 30,000 to 50,000 of these neurons in the brain, they present a unique research opportunity which could yield valuable clues as to why they are vulnerable and how their degeneration during ageing causes disease, explained Zhang.

The Centre’s ambitions extend beyond research models. Besides using stem cell-derived neurons to develop a model system to study neurodegeneration and ageing, the team aims to use their techniques to find treatments for serious injuries such as those caused by a stroke.

For example, they demonstrated that stem cell-derived neurons can be successfully transplanted into the area of the brain damaged by a stroke. The key to their success was a chemical cocktail of proteins and drugs that protects the nascent neurons from the highly inflamed environment. Fully shielded, the neurons not only survived but proliferated, successfully repair damaged brain tissues and matured into functional neurons.

“Our transplantation method has proven that cultivated cells can mature to become functional neurons and potentially integrate into brain circuitry in conditions such as stroke, spinal cord injury and Parkinson’s disease,” said Dr Wang Zhifu, lead author of the study, which was published in Advanced Science, and a research fellow with the Programme. “The human brain has a very limited capacity to regenerate so there is a need for more effective treatment for neurological diseases.”

This method has since been licensed and the team plans to commence preclinical safety studies next—a prospect made possible by the generous $5 million gift by the GK Goh family in honour of Mr GK Goh, Founder and Executive Chairman of G.K. Goh Holdings to establish the GK Goh Centre for Neuroscience.

Referring to the gift as “catalytic” during a media briefing to share the first breakthroughs that form the foundation of the Centre, Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS elaborated on its impact: “It propelled our researchers like Suchun to rapidly advance in this area, a quantum leap that would not have been possible otherwise.”

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Zhang and his collaborators have also used the technology to develop cell-based therapies for Parkinson’s disease. In those earlier studies, they used stem cell-derived dopamine neurons to regenerate damaged brain tissues in preclinical models of Parkinson’s disease.

The team is now seeking approval from US regulators to start human safety clinical trials.

“The possibilities of this novel technology are boundless,” said Professor Thomas Coffman, Dean of Duke-NUS. “Professor Zhang and his team have cultivated various functioning neurons, including those in the brain, eye and spinal cord. They have also collected a comprehensive spectrum of biological samples for unravelling the mysteries of brain ageing and developing new therapies for otherwise incurable brain conditions. We are immensely grateful to the GK Goh family for their support in this ground-breaking endeavour.”

Cutting the ceremonial ribbon are (L – R): Prof Thomas Coffman, Dean of Duke-NUS, Mrs Goh Yew Lin, Mr GK Goh, Duke-NUS Governing Board Chairman Mr Goh Yew Lin and Prof Zhang Suchun at the newly established GK Goh Centre for Neuroscience, joined by representatives from Duke-NUS and NUS // Credit: Norfaezah Abdullah, Duke-NUS

Up and coming at the GK Goh Centre for Neuroscience

Ms Yvonne Yen, a fourth-year MD-PhD student, is harnessing the same technology to produce endothelial cells that are found on the lining of blood vessels.

By using the cells as a model system to study changes in the blood vessels during Alzheimer’s disease, Yen aims to uncover factors underlying the changes in the vasculature that cause decreased blood flow to certain regions of the brain during the disease.

Side by side pictures of cells as seen under the microscope. The left side shows endothelial cells from a healthy individual while the right side shows those from a patient with Alzheimer's disease

Endothelial cells grown from a healthy individual (left) and from a patient with Alzheimer’s disease (right) // Credit: Zhang Suchun, Duke-NUS