Dr. Vo Van Giau, 38 years old, and his colleagues discovered the key gene that prevents brain cell death, paving the way for the diagnosis and treatment of Alzheimer’s disease.
Alzheimer’s disease (AD) is a brain disease caused by abnormal biochemical phenomena in the brain, leading to the death of brain cells and affecting the patient’s cognitive ability. Currently, only 6 drugs including Tacrine, Donepezil, Carbalatine, Galanthamine, Memantine and Lecanemab have been approved by the FDA for clinical use in the treatment of Alzheimer’s disease. However, the drugs can only help reduce symptoms but cannot completely eliminate the core pathogenesis related to the accumulation and dysfunction of two main proteins: beta-amyloid (Aβ) and Tau.
According to Dr. Giau, Sanford Burnham Prebys Medical Discovery Institute (USA), one of the barriers to finding effective treatments for Alzheimer’s disease is limited understanding of the underlying biological causes of abnormalities in the pathogenesis of the disease.
As project leader, he and his research team at Sanford Burnham Prebys Medical Discovery Institute have found and demonstrated the role of genes in the retromer complex, including the SORLA gene, in preventing the formation of Aβ proteins through animal models. This is also the first time in the world that scientists have demonstrated that this gene has an effect on inhibiting the formation of Tau proteins. The research team has also shown that retromer and/or SNX27 dysfunction disorders are closely related to the pathogenesis of the disease.
He explained that the abnormal accumulation of senescent plaques of Aβ and Tau proteins may contribute to inflammation, neurodegeneration, and cognitive decline in Alzheimer’s disease and other neurodegenerative conditions. Among them, SORL1 (the gene that encodes SORLA) is one of many genes that are associated with Alzheimer’s risk. Therefore, this discovery helps biochemists better understand how SORLA affects Aβ and Tau proteins.
“Accurate prediction of Alzheimer’s disease progression based on genetic variants in the retromer gene cluster including SORLA helps improve clinical trial design, opening up opportunities to develop new, more personalized diagnostic and treatment methods,” said Dr. Giau.
To pioneer this promising approach, the team developed and applied a xenotransplantation system of microglia and neurons, by injecting hematopoietic progenitor cells (HPCs) and neural progenitor cells (NPCs) into the brains of immunodeficient mice immediately after birth (P0/P1). This is the stage when the blood-brain barrier is not fully developed and the brain is more receptive. The goal of this transplantation is to explore the characteristics, roles, and potential mechanisms of genetic variations in both major disease models, Tau and Aβ.
To translate the results of basic research, the group initially found a number of compounds that protect and enhance gene expression on SNX27/retromer and SORLA through experimental models on stem cells and animals. From there, they aimed to prepare derivatives that have neuroprotective effects, preventing and inhibiting the formation of Aβ and Tau in the brain.
The project, recently funded by the Conrad Prebys Foundation, aims to screen and develop compounds to prepare neuroprotective derivatives.
Protective and functional enhancement of retromer genes may be potential therapeutic strategies against aging and cognitive decline. Photo: Researchers
Professor Kevin Yip of Sanford Burnham Prebys assessed that “the work has the potential to help people affected by Alzheimer’s disease, as well as Tau-related pathologies (tauopathies) such as frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy”.
Dr. Giau began pursuing research related to health sciences, including diagnosis and treatment of common diseases in the elderly including Alzheimer’s since 2014 when he received a full scholarship for the PhD program in Biomedical Engineering at Gachon University, Korea. Over the past 10 years, he has had many widely applied projects such as developing a Kit for disease detection and screening at many major hospitals in Korea, designing a gene map to diagnose Alzheimer’s disease…
He has published 90 ISI articles, 7 international monograph chapters and 2 patents on Alzheimer’s disease diagnosis solutions. He has also received many scholarships and awards in science and technology such as Outstanding Scientist 2017 from the Korean BK21 Foundation; Young Scientist Award from the Malaysian Society of Biochemistry and Molecular Biology in 2019; Golden Globe Science and Technology Award 2019, Conrad Prebys Award to honor outstanding achievements in the fields of medical research, arts and education in the US in 2023…