Prof. Gary Tse (third from the left in the picture) with other co-principal investigators and expert advisory board members from the University of Cambridge and the City University of Hong Kong.
Alzheimer's disease (AD) is a type of dementia that affects patients' memory, thinking, and behaviours. According to the Alzheimer's Association, there were more than 55 million people worldwide living with AD and other dementias.[1] The primary cause of AD is the production of a misfolded protein – beta-amyloid – in the neuron, leading to inflammation in the brain and neuron cell death. Medications only facilitate temporary cognitive retrieval for patients but fail to stop the disease progression. Also, therapeutic challenges, such as the blood-brain barrier and autoimmunity, have bogged down AD drug development.
Gene therapy has drawn attention as a potential treatment for AD, by targeting specific genes in the neurons involved in misfolded protein formation and reducing the production of such protein within a tolerable range. The benefits of a smaller molecular size, lower cost, quicker acquisition and higher specificity make gene therapy capable of overcoming most existing challenges in brain-targeting drug development.
To develop gene therapy for treating AD, Hong Kong Metropolitan University (HKMU) has taken part in a collaborative project with industry, City University of Hong Kong (CityU), the University of Hong Kong, and members from overseas. The project aims to develop a new drug for AD treatment based on a type of molecule called siRNA (small interfering RNA) which can help target specific genes related to AD pathology and selectively inhibit the expression of genes related to beta-amyloid. This project will adopt a multidisciplinary approach to drug discovery, combining bioinformatics, rational drug design, cellular and animal experiments.
As the principal investigator of the research study, Prof. Gary Tse addresses his collaborators at the opening ceremony, expressing gratitude and inspiring a collective commitment to excellence in the innovative project aimed at finding a cure for Alzheimer's disease.
This collaborative project is jointly funded by the industry and government, and is supported by an international advisory board comprising members from the Queen Mary Hospital in Hong Kong, University of Cambridge, Imperial College London, University College London and National University Health System of Singapore.
As one of the leading parties, HKMU contributes to the project in areas of scientific leadership, strategy, and execution. The HKMU team plays a major role in the rational design of siRNA candidates that could be used to target the BACE1 gene, an enzyme that catalyses the cleavage of amyloid precursor protein, leading to the production of beta-amyloid. The team is also responsible for identifying and optimising the method for penetrating the blood-brain barrier whilst reducing side effects from immunogenicity and will use lipid nanoparticles to achieve this.
The project team anticipates that this new method can achieve reductions in beta-amyloid levels and improve cognitive function in preclinical studies. The project outcomes will serve as a robust foundation for clinical trials, bringing us one step closer to a potential cure for AD, thereby offering new hope to millions of patients and their families.
[1] https://www.alz.org/alzheimer_s_dementia
