Alzheimer's disease is the most prevalent form of dementia, profoundly impacting patients' memory, cognition and self-care ability. Unfortunately, no cure has been identified so far for this devastating condition. A scholar from the School of Nursing and Health Studies at Hong Kong Metropolitan University (HKMU) has co-led a cross-university, multi-disciplinary, international research team to develop a new drug for Alzheimer's disease by combining nanotechnology and gene therapy. The drug functions by inhibiting the production of harmful proteins in the patient's brain, effectively suppressing the progression of the disease and alleviating its debilitating symptoms.

According to the Government's Mental Health Review Report in 2017, an estimated nearly ten thousand people in Hong Kong suffer from dementia, accounting for nearly one-tenth of the elderly population. Among all forms of dementia, Alzheimer's disease is the most prevalent, comprising 65% of reported cases.

Alzheimer's disease is a condition in which brain function declines due to damage to nerve cells. It is characterized by the formation of neural plaques and neurofibrillary tangles, accompanied by neuron loss, particularly synaptic loss. Within the plaques, there is accumulation of harmful proteins called beta-amyloid (β-amyloid), which leads to deterioration and death of brain cells. The disease affects a wide range of cognitive functions, including memory, comprehension, language, learning, numeracy and judgment. As the brain functions further deteriorate, the patients' ability to look after themselves becomes greatly impaired, requiring long-term care and support from their family.

Currently, the drugs used to treat Alzheimer's disease primarily address symptoms such as memory loss, cognitive impairment and diminished comprehension. While these medications can temporarily improve cognitive function in patients, they cannot prevent the disease from worsening over time. Medical researchers have yet to identify a cure for this devastating disease.

HKMU School of Nursing and Health Studies Associate Dean (Innovations and Research) Prof. Gary Tse has conducted related medical research with a team of scholars from City University of Hong Kong, The University of Hong Kong, University of Cambridge's School of Clinical Medicine, Imperial College London, University College London, National University of Singapore and Queen Mary Hospital of Hong Kong. The team members have backgrounds such as basic and clinical sciences, medicine and pharmacy. By combining innovative nanotechnology and gene therapy, the research team has developed a novel approach using small interfering RNA (siRNA) to inhibit the production and accumulation of beta-amyloid proteins (β-proteins) in the patient's brain.

Patients with Alzheimer's disease continue to produce harmful β-proteins in the brain, and the accumulation of these proteins is a major driver of disease progression and deterioration. To address this, the research team has developed a gene therapy approach, introducing siRNA into the patient's body through application of a drug. The siRNA targets the gene responsible for causing Alzheimer's disease, preventing the brain from producing the harmful β-proteins, thus reducing their accumulation. By disrupting this mechanism, the therapy can slow the progression of cognitive decline and the development of Alzheimer's disease.

To ensure the safe and effective delivery of the therapeutic siRNA to the brain cells, the research team has explored a novel nanotechnology approach using lipid nanoparticles, which are designed to penetrate and cross the blood-brain barrier, while evading attack from the patient's immune system. This allows the siRNA drug to enter the brain cells more stably and exert its therapeutic effects. The research team has employed advanced bioinformatics tools to design different siRNA gene sequences and conducted rigorous cellular experiments and animal studies. By optimising the therapeutic effects through stringent testing, the team aims to minimise potential side effects.

Prof. Gary Tse of HKMU said he hoped the research would establish a solid foundation for future clinical studies on Alzheimer's disease. He commented, “This research leverages innovative technology to address Alzheimer's disease, for which there is currently no cure or prevention. By targeting the root cause of the disease through siRNA gene therapy, we believe that there is new-found hope for patients and their families worldwide.”