Scientists from the University of Bath have made a significant breakthrough in understanding the role of the Angiogenin (ANG) gene in age-related neurodegenerative diseases such as frontotemporal dementia (FTD), motor neuron disease (MND), and Parkinson's disease. Their research has revealed that mutations in the ANG gene cause stem cells to delay their differentiation into specialized nerve cells, leading to neurodevelopmental defects.

The study, published in the Journal of Pathology, highlights the crucial role of the ANG gene in the development of nerve cells. In its mutated form, ANG causes stem cells to remain in an undifferentiated state for longer periods of time than normal. Laboratory experiments showed that this delay in differentiation resulted in profound neurodevelopmental defects in the adult nerve cells.

Dr. Vasanta Subramanian, who led the research from the Department of Life Sciences, suggests that this finding implies that defects occurring during early development may predispose nerve cells to degeneration later in life. These findings offer new insights into the potential for early intervention in these debilitating diseases.

Notably, the research also uncovered an important protective function of the healthy form of the ANG gene. In contrast to the mutated form, the healthy ANG gene helps safeguard nerve cells against damage, degeneration, and impaired function. The mutated form of the gene, on the other hand, makes nerve cells more vulnerable to stress, leading to premature death.

To further investigate the impact of ANG mutations, the researchers studied a family affected by frontotemporal dementia and motor neuron disease. They grew "mini-brains" in the lab, three-dimensional structures composed of human stem cells. The mini-brains served as a realistic model to study disease development and screen potential treatment options. In the family members carrying the ANG mutation, the researchers observed significant neurodevelopmental defects in the mini-brains.

Dr. Subramanian envisions a future where individuals susceptible to these diseases can be identified, screened for genetic mutations, and offered early-intervention gene therapy to address the defects. However, further research is needed to fully understand the mechanisms by which ANG protects cells and its role in stem cell function.

This groundbreaking research was made possible thanks to grants from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), BRACE, and the Wellcome Trust VIP award. The findings hold promise for future treatments aimed at slowing down or even halting the progression of frontotemporal dementia and related neurodegenerative diseases.

The CEO of BRACE, Chris Williams, commended Dr. Subramanian's research, stating that the better understanding of the Angiogenin gene and its connection to frontotemporal dementia could potentially have a significant impact on reducing the impact of the condition. Frontotemporal dementia, which predominantly affects individuals aged 45-65, can have devastating consequences during middle age.

Dr. Jessica Eddy, the NC3Rs Regional Programme Manager, praised the study for its use of innovative mini-brain "organoids" and the novel insights they provide into neurodegenerative diseases. She emphasized the importance of such cell-based alternatives in advancing research and reducing reliance on animal models.

This latest research breakthrough brings new hope for the early detection and intervention of age-related neurodegenerative diseases, potentially leading to improved treatment options and a better quality of life for affected individuals.