The Chinese Communist Party’s third plenum last month set the country’s long-term direction on economic policy, with strategic industries such as AI and biomedicine targeted. Traditional enterprises will also be encouraged to transform with the help of technology. In this five-part series, the Post looks at innovations by up-and-coming Hong Kong scientists who are already making waves and may even be the next big winners like tech giants DJI and SenseTime.
Amy Fu Kit-yu recalls the sheer joy when she and her team of researchers discovered after years of effort that injecting a certain protein into mice with Alzheimer’s disease reduced toxic substances believed to be responsible for the condition. “We gathered the whole lab to look at the test results and asked them what they could observe,” said Fu, a life science research professor at the Hong Kong University of Science and Technology (HKUST). “I was extremely happy to find out the pathway.
This is why we are addicted to scientific research.” Fu, a leading researcher in the team headed by university president Professor Nancy Ip Yuk-yu, started her quest about 10 years ago amid a global race among scientists to find a cure for Alzheimer’s disease, a devastating neurodegenerative condition that affects more than 50 million people worldwide. The team won two top prizes at the 49th International Exhibition of Inventions Geneva in April, with Hong Kong sending its largest delegation yet this year.
The team’s research was recognised for opening up new possibilities for a potential cure for Alzheimer’s disease, providing a safer, simpler and less invasive approach compared with traditional ones. Fu was joined by two talented young scientists – research associate Stephanie Duan Yang-yang and assistant scientific officer Danise Au, for a recent interview with the Post at their pristine lab nestled in the Hong Kong Centre for Neurodegenerative Diseases in the Hong Kong Science Park. Chinese President Xi Jinping visited the lab in 2022, with Ip, a renowned neuroscientist and Alzheimer’s disease expert, introducing their research and other projects to him.
03:08 HKUST scientists look back on decade-long journey to find cure for Alzheimer’s disease Duan, who came to Hong Kong from Yunnan province in 2013 to study for a bachelor’s degree in biochemistry and cell biology, is a research assistant professor at the age of 29. “Working on the research and witnessing sST2 [a blood protein found to be a culprit causing Alzheimer’s disease] being optimised as a target is like watching a baby growing up,” said Duan, who has been involved in the project for four years. “I feel very happy to see its growth.
” Au, who graduated with a degree in medicine from the University of Hong Kong in 2021, said she decided to shift her career path to focus more on research and joined the team a year ago. “Clinicians are a very practical and immediate method to help patients, but there are limitations in clinical medicine and there is only so much you can do for the patients,” the 26-year-old said. “This is where research is able to step in to fill this gap to advance further so that we can treat patients better in the future.
” The Hong Kong Mental Morbidity Survey for Older People conducted by the Chinese University of Hong Kong last year found 10 per cent of residents aged 70 and above suffered from dementia. According to the Department of Health, Alzheimer’s disease is the most common cause of dementia. Based on a study by the university in 2016, 300,000 people could have dementia by 2039.
An overseas study last year estimated global dementia cases could reach 153 million by 2050. Scientists around the world are working hard to discover how to delay symptoms or even to cure the disease, which is adding to the burden of many fast-ageing countries. Last year, Lecanemab, an infusion therapy produced by American biotechnology company Biogen, became the first traditionally approved treatment for Alzheimer’s by the US Food and Drug Administration (FDA).
It is not a cure but it targets the underlying biology of the disease and slows its progress for early stage patients, according to the Chicago-based Alzheimer’s Association, the world’s largest non-profit funder of research into the condition. It costs a patient about US$26,500 a year to receive the therapy. Another drug that can slow the disease’s progression is Donanemab, developed by US pharmaceutical company Eli Lilly, which also clears amyloid plaques, a protein associated with the condition, from the brain.
The FDA approved it last month to treat patients with mild cognitive impairment or mild dementia. Eli Lilly also produces another drug named Remternetug, which is expected to perform better than Donanemab. Clinical trials are being conducted on it and it is yet to be approved by the FDA.
The HKUST research team recently said that after nine months of effort, it had finally screened 300,000 chemical compounds and selected around 10 candidates with potential therapeutic value. It has now entered the stage of a preclinical study, before the potential drug can be tested on people. The breakthrough was made after two major discoveries.
First, a protein named Interleukin 33 (IL-33) can help to activate immune cells in the brain, known as microglia, to clear toxic molecules named Aβ, which are responsible for causing Alzheimer’s disease. Second, a blood protein called soluble ST2 (sST2) disrupts microglia’s role in clearing the toxic substance. Fu said that back in 2013, when the team decided to study IL-33, the global research community only knew it was “a protein highly expressed in the brain”.
“When the body encounters some injuries or infection, IL-33 will alert the immune system and tell it to start working to protect the body. But no one knew about its function in the brain,” she said. After almost 10 years of study, the team discovered it helped to activate microglia to clear the toxic substance.
The team also demonstrated that an IL-33 injection could improve the memory performance in the mouse model with the disease. Separately, the team also found that when the sST2 level increases in the blood and the brain during ageing, it will upset the activities of IL-33, which will fail to remove the toxic substance. They had also studied the brains of deceased patients and found that those with certain genetic information had lower sST2 levels, thus less risk of Alzheimer’s disease.
Fu said the discovery meant reduced sST2 levels could be a potential therapeutic approach which only required manipulation of the blood protein, providing a “simpler and safer” approach compared with other options that targeted the brain. Another mice model study also found that reducing sST2 could decrease the chance of Alzheimer’s disease being developed, she said. The team is now looking into two approaches for developing the new drug – chemical and gene therapy.
“For the chemical approach, we did a huge study where we screened 300,000 compounds and ended up with around 10 candidates,” Fu said, adding that it took them nine months. “We have demonstrated their efficacy in reducing sST2 in the cell system. Next step, we will prioritise the candidates for development based on their activity on reducing Alzheimer’s disease pathology in the diseased mouse model.
” Fu said they were currently undergoing a preclinical study where they aimed to optimise the compounds to ensure the best efficacy in animals, as well as safety. “Our major work currently is to move these compounds to mice, for example, by oral delivery, to see whether it can really suppress sST2 levels,” she said. They had seen “encouraging” preliminary data, while there was still “a lot of room for optimisation”, she said.
Fu said after modifying the compounds, they would need to ensure their stability and safety, adding that she wished to complete the preclinical study in three years before entering the clinical trial. The gene therapy approach, Fu said, targeted the sST2 gene and they were able to see reduced levels of the blood protein in mice. She said she hoped the preclinical study could be finished in “a few years”.
Fu said with their “promising” discoveries, they could potentially develop a drug that could be a cure for Alzheimer’s disease that could reduce sST2 levels. “It can be a disease-modifying therapy, instead of a symptom-relief approach,” she said. “For the drug to be a cure, it depends on whether we can identify a patient at an early stage where the disease can be modified.
” The team had also developed a blood test that could identify the early stages of Alzheimer’s disease with an accuracy rate of nearly 90 per cent. The drug and the test could “complement each other”, Fu added. “For our future plan, we definitely would like to understand better how soluble ST2 causes the impaired microglial functions in Alzheimer’s disease [affected] brains.
That is our major goal,” she said. “We have been putting a lot of effort into understanding how soluble ST2 acts on the immune cells. Understanding its mechanism will definitely increase the chance of success in drug development.
This will be a major focus of our basic research studies.”.
