Malaysian neuroscientist receives two international research grants, aims to find a way to prevent Down syndrome

Many years ago, as an undergraduate student, neuroscientist Dr. Michael Ling met someone who worked with children with Down’s syndrome at Kiwanis Malaysia.

The latter looked after the children and provided them with special education. But what was unique about her was that she herself had Down’s syndrome.

“Not only was she able to understand, lead and follow the conversations well, but she was very familiar with the work flow at the center and looked after the children there very well,” Ling recalls.

“It was the first time that I had such a close interaction with a person with Down syndrome and it really changed my perception of her,” admitted the 42-year-old man from Melaka.

Ling said her experience opened her eyes to the importance and benefits of early special education and medical care for children with Down syndrome, and more importantly, how they can contribute to society and lead. a normal life.

“This meeting sparked my interest in studying the disease further,” said Ling, who went on to receive her doctorate in developmental neurogenetics from the University of Adelaide, Australia.

The Associate Professor of Developmental Neurogenetics at the Faculty of Medicine and Health Sciences at Universiti Putra Malaysia (UPM) is also a postdoctoral researcher in neurodegenerative and neuropsychiatric disorders at Harvard Medical School.

Ling was recently awarded the Return Home Fellowship from the International Brain Research Organization and the Return Home Fellowship from the International Society for Neurochemistry.Recently, he was awarded two renowned research fellowships: the Return Home Fellowship from the International Brain Research Organization (€ 20,000 / RM95,000) and the Return Home Fellowship from the International Society of Neurochemistry (US $ 10,000 / RM42,000).

Grants are awarded to support internationally trained neuroscientists who return to their home countries to continue their research.

To be eligible, the fellow must write a research proposal and provide letters of support from the home institution (UPM) and the host institution (Harvard Medical School) for knowledge transfer, explained Ling, who was surprised and delighted to receive the grants.

Ling’s proposal was to study the brain development of Down syndrome using brain organoids (miniature organs artificially grown in vitro that resemble the brain) or “mini brains on a plate.”

Down syndrome is caused by the presence of an extra copy of the 21st chromosome (or trisomy 21), leading to physical and mental development delays and disabilities.

Ling is determined to find out how having that extra chromosome leads to complications in growth and development.

“Understanding the underlying molecular and cellular mechanisms caused by the extra genetic material would allow us to formulate the correct therapy up front, in particular, finding a way to reverse intellectual disabilities in children with Down’s Syndrome while they are still.” in the womb without any harm to the mother or the child, ”he explained.

Making breakthroughs in neuroscience

The youngest of six siblings, Ling lives in Puchong, Selangor with his wife, Dr Cheah Pike See, who also works at UPM as an associate professor in anatomy and neurobiology.

Ling (right) and his wife Cheah lead the Neurobiology and Genetics group at UPM. Ling (right) and his wife Cheah lead the Neurobiology and Genetics group at UPM.The couple lead the Neurobiology and Genetics group at UPM, where Ling heads the Medical Genetics Unit at the Faculty of Medicine and Health Sciences.

“I am grateful that my family has supported my work and my research so much.

“The scholarships will help me launch my research into Down syndrome in Malaysia, and I consider myself very lucky to have received them.

“Research grants are very difficult to come by during the pandemic as most of the resources have been diverted to the fight against Covid-19,” he said.

Both grants are administered by UPM and Ling aims to use the funds to establish a facility in the Stem Cell Research Laboratory of the Faculty of Medicine and Health Sciences to cultivate brain organoids for Down syndrome, a model which will allow him to find answers to questions about Down Syndrome.

“My team is very interested in finding out how the extra chromosome can lead to intellectual disability.

“Throughout their development, children with Down’s syndrome have smaller head sizes and smaller brains than their unaffected peers.

“The number of neurons and their ability to branch out and connect to each other is also less, and the brain with Down’s syndrome experiences greater stress throughout its life, leading to accelerated neurodegeneration or the early onset of the disease. dementia, ”Ling explained.

“We are determined to find a way to restore this neuron-astrocyte imbalance that occurs in the first month of pregnancy.

“We would like to find a treatment, such as a drug or supplement, that can be given to high-risk women who are planning to conceive so that we can prime and modulate the fate of brain cells in the affected embryo / fetus to restore the neuron-astrocyte without endangering the mother or the embryo / fetus, ”he added.

“It will help reduce the risk of Down syndrome. “

Ling explained that there are many challenges in the field of neuroscience.

“While neuroscience has advanced tremendously over the past decades, the human brain is still a mystery and no cure has been found for many brain disorders at this stage,” he said, adding that the lack feasible models make it difficult to study human neurological disorders.

“But as neuroscientists we are like part of a larger whole, and I am happy to be able to contribute to the understanding of the human brain or the molecular pathology of neurological disorders.

Ling (third from left) with his wife, Cheah, (fourth from left) and members of their search team.  Photos: Dr Michael LingLing (third from left) with his wife, Cheah, (fourth from left) and members of their search team. Photos: Dr Michael Ling

“With the new technology that I have mastered, our group can develop a mini-brain derived from a patient on a dish to recap the development, onset and progression of the disease.

“This fascinating technology leading to the advancement of brain organoids and genome editing (genetic engineering) will revolutionize the way we do neuroscience research,” he said.

Ling said his ultimate goal is to eventually be able to reverse the imbalance in the neuron-to-glial cell ratio in individuals with Down’s syndrome so that they will one day have the same intellectual capacities as other individuals.

“When we have more neurons, we expect them to branch out and connect better, which leads to better learning abilities and better memory retention.

“But while the method focuses on the early modulation of embryos with Down syndrome early in development, studies can and should also be conducted on the beneficial results of the same approach in early-onset leukemia and dementia. “, did he declare.

“At Harvard Medical School, I had the privilege and opportunity to learn the revolutionary CRISPR-Cas9 gene editing technology, a molecular tool used to cut and delete one or more DNA sequences in the genome. of any living organism (using organoids).

“This means that genetic disorders can be cured by changing and restoring inherited (defective) DNA sequences to functional sequences such as changing a mutation in the APOE-e4 gene, which increases the risk by 15 times. to develop Alzheimer’s disease, ”he said. noted.

“Translating the results of our research into animal models in humans requires different stages of clinical trials.

“But given the good research funding, well-equipped facilities and great talent, I am confident that we can see the ideas translated into clinical practice over the next 10 to 15 years,” Ling concluded.

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