CU Medicine and the CUHK’s Gerald Choa Neuroscience Institute have achieved a significant (GCNI) “bench-to-bedside” advancement by translating discoveries in ageing biology into a potential new treatment strategy for stroke, which pioneers GLP-1 drug class to improve severe stroke recovery. The team will launch a Phase III study to further establish the efficacy and safety of GLP-1RA.

(From left) Dr Ko Ho, Director of GCNI and Associate Professor in the Department of Medicine and Therapeutics at CU Medicine; Professor Thomas Leung Wai-hong, Head of the Division of Neurology and Lee Quo Wei Professor of Neurology in the Department of Medicine and Therapeutics at CU Medicine; and Dr Bonaventure Ip Yiu-ming, Assistant Professor in the Department of Medicine and Therapeutics at CU Medicine.

Researchers from The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) and the Gerald Choa Neuroscience Institute (GCNI) have achieved a significant “bench-to-bedside” advancement by translating discoveries in ageing biology into a potential new treatment strategy for stroke.

The research team first demonstrated in experimental studies that enhancing glucagon-like peptide-1 (GLP-1) signalling can counteract key hallmarks of ageing across multiple organ systems, including the brain. Building on these findings and the team’s previous research on glucagon-like peptide-1 receptor agonists’ (GLP-1RA) effect on cerebrovascular protection, they conducted the world’s first randomised clinical trial to evaluate GLP-1RAs in patients undergoing reperfusion therapy for severe ischaemic stroke caused by large vessel occlusion (LVO). The results showed better outcomes in some patients, indicating potential efficacy and paving the way for future large-scale studies on neuroprotection. The findings have been published in the internationally renowned journals Cell Metabolism and Nature Communications.

From ageing biology to stroke therapy

GLP-1 is a peptide hormone produced naturally in the gut and brain that regulates bodily functions. GLP-1RAs, which are designed to mimic its action, are already widely used in the treatment of diabetes and obesity. The team’s previous studies demonstrated the anti-neuroinflammatory and blood-brain barrier stabilising effects of GLP-1RAs in rodent models, underscoring their potential neuroprotective role in stroke.

A preclinical study led by Dr Ko Ho, Director of GCNI and Associate Professor in the Department of Medicine and Therapeutics at CU Medicine, demonstrated that GLP-1RAs can counteract key biological processes associated with ageing. Using advanced multi-omics technologies, the team identified widespread molecular effects across multiple organs, including the brain and heart, suggesting that GLP-1RAs may exert broad protective effects when it comes to brain health and systemic ageing. These findings provided a powerful scientific rationale for investigating GLP-1RAs as a potential therapy for neurological diseases such as stroke.

Dr Ko says that GLP-1RAs can counteract key biological processes associated with ageing, exerting widespread molecular effects across multiple organs—including the brain and heart—which are even more pronounced in older animals. These findings provide a strong scientific rationale for investigating GLP-1RAs as a potential therapy for neurological diseases such as stroke.

Professor Thomas Leung says the studies show GLP-1RA can have anti-aging and neuroprotective effects. However, prevention of stroke and neurodegenerative diseases is closely related to healthy lifestyle. By managing the three highs (blood pressure, blood sugar, and blood lipids), maintaining a healthy diet, exercising regularly, and developing good lifestyle habits, one can already help maintain good brain health.

A novel approach to protecting the brain after strokes

Stroke remains one of the leading causes of death and long-term disability worldwide. In patients who have suffered from LVO strokes, endovascular thrombectomy can restore blood flow to the brain. However, even after successful procedures, many patients continue to experience poor neurological outcomes.

Professor Thomas Leung Wai-hong, Head of the Division of Neurology and Lee Quo Wei Professor of Neurology in the Department of Medicine and Therapeutics at CU Medicine, explained: “While endovascular thrombectomy is highly effective at reopening blocked vessels, many patients still experience significant disability due to reperfusion injury and delayed treatment. This highlights the urgent need for adjunct neuroprotective therapies that can protect vulnerable brain tissue during and after treatment to maximise efficacy.”

Clinical trial demonstrates safety in severe LVO stroke patients

Building on the team’s multi-omics laboratory findings, the research team, led by Dr Bonaventure Ip Yiu-ming, Assistant Professor in the Department of Medicine and Therapeutics at CU Medicine, conducted the first Phase 2 randomised clinical trial to translate these biological insights into patient care. The trial conducted by CU Medicine involved 140 patients with severe LVO stroke from Prince of Wales Hospital and a stroke centre in China, who had undergone thrombectomy. Patients were randomised to receive either semaglutide, a GLP-1RA, in addition to standard therapy, or standard therapy alone.

The results showed that 56.5% of patients with severe LVO stroke who received semaglutide achieved good functional recovery at 90 days, which is similar to the 54.9% in the standard therapy group, indicating comparable efficacy between the two. No severe adverse events were attributed to the drug, and key safety outcomes, including death, malignant brain oedema and intracranial haemorrhage, were similar between the two groups, indicating that semaglutide is safe and well-tolerated in acute stroke patients.

Exploratory analyses suggested a potential benefit in patients who did not receive intravenous thrombolysis before thrombectomy, with a 20% higher proportion of patients treated with semaglutide achieving favourable neurological recovery compared to standard therapy alone.

Dr Ip commented: “These findings provide early clinical evidence supporting the safety of GLP-1RAs in acute stroke settings, suggest potential benefits in selected patient groups and pave the way for a larger, phase 3 randomised trial to confirm the drug’s neuroprotective potential.”

Dr Ko remarked: “Our work represents an important step in translating fundamental ageing research into clinical application. By linking multi-omic laboratory discoveries with patient-based investigation, our findings highlight the potential for GLP-1RAs to be repurposed as a new therapeutic indication in stroke treatment.”

Dr Bonaventure Ip says that this study has preliminarily shown that GLP-1RA is more effective in patients who have not received intravenous thrombolysis therapy than in those who have. However, the underlying reasons remain unknown, and the team will conduct further research to better understand the mechanism.

In 2024, Mr. Lee (right) suddenly felt unwell and was found to have hemiparesis and aphasia. He was diagnosed with large vessel occlusion stroke. Mr. Lee received two doses of GLP-1RA treatment and underwent thrombectomy, which successfully reopened 90% of the previously occluded vessels. His quality of life after recovery is similar to that before the stroke.