CUHK transforms ginkgo compound to promising drug candidate targeting brain inflammation to combat strokes and Alzheimer’s disease
A research team at The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine), has employed precision “molecular editing” on a natural compound found in ginkgo trees to develop a potent synthetic drug candidate, BB56, capable of suppressing harmful brain inflammation. Published in the international journal Advanced Science, the breakthrough sheds new light on the discovery of neuroprotective agents for developing new medicines to combat neurological conditions such as stroke and Alzheimer's disease.
The CU Medicine research team led by Professor Billy Ng Wai-lung, Associate Professor from the School of Pharmacy (front row, centre).
Neurological disorders affect more than three billion people globally, representing over 40 percent of the world’s population[1]. Neuroinflammation, triggered when a dysregulated immune system turns the brain’s protective mechanisms into destructive forces, is increasingly recognised as an important contributor to the major disorders. Developing therapeutics capable of interrupting this inflammation process is vital to preserving essential cognitive functions, including memory, motor skills and the ability to live independently.
Creating promising drug candidate through molecular editing
Bilobalide, a natural compound found exclusively in ginkgo leaves and seeds, is known for its reported neuroprotective and anti-inflammatory properties that may help protect nerve cells. However, its complex and chemically fragile structure makes its systematic modification into a viable pharmaceutical drug difficult.
To overcome these challenges, the research team led by Professor Billy Ng Wai-lung, Associate Professor from the School of Pharmacy, CU Medicine, adopted a strategy of “molecular editing”. The chemical modification technique can selectively remodel key parts of bilobalide’s complex structure while preserving its distinctive core, allowing researchers to create molecules that are more stable and easier to modify.
Building on a 2024 study that created the precursor compound BB10, the team developed BB56, an optimised derivative featuring strategic fluorine insertion. This structural addition significantly boosts cellular potency, resulting in more effective inhibition of the inflammatory process.
Professor Ng remarked: “Molecular editing opens new possibilities for drug development. We can create and compare a family of related molecules, identify which chemical changes improve their activity and direct further work towards the strongest leads. The approach allows researchers to develop original molecules systematically from a natural starting point and explore their potential as treatments for stroke and neurodegenerative diseases such as Alzheimer’s disease.”
Uncovering the anti-inflammatory mechanism to inform drug design
In preclinical experiments using lab-cultured microglia, the brain's primary immune cells, and larval zebrafish models with induced brain inflammation, the research team successfully validated BB56’s anti-inflammatory efficacy and decoded its underlying biological mechanism.
Overactivated microglia can elevate the release of prolyl endopeptidase (PREP), an enzyme that normally helps regulate and maintain brain function. However, when present at excessive levels, PREP may disrupt protective signalling and promote inflammatory responses.
The research team found that BB56 can bind to and inhibit PREP, effectively blocking its activity. They further showed that by inhibiting PREP, BB56 reduces the production of inflammatory molecules, dampens inflammation-related signalling pathways and suppresses the overactivation of microglia. These findings highlight BB56's potential as a promising lead compound for the development of new medicines for neuroinflammatory disorders. The research team has filed patent applications in China and the United States and through the World Intellectual Property Organization for their discoveries.
Professor Ng added: “This study demonstrates the translational journey from molecular editing and biological discovery to target identification, optimisation and in vivo validation. Rather than simply studying what nature provides, we aim to use techniques in modern chemistry and biochemistry to redesign natural molecules into new therapeutic leads. Our long-term ambition is to advance original drug discoveries made here in Hong Kong into new medicines that benefit patients suffering from neurological diseases worldwide.”
[1] According to the Global Status Report on Neurology released by the World Health Organization in October 2025.
