Treating age-related diseases such as dementia is a challenge for medicine. On the one hand, more and more people are affected by such diseases due to longer life expectancy. On the other hand, there is a lack of effective remedies and therapies, especially for neurodegenerative diseases.
This is where brain organoids like the one shown in cross section above come into play. They make it possible to grow customized mini-brains from stem cells. Depending on the source cells used, it is possible to specifically examine the impact of certain gene mutations and potentially disease-causing genes.
Using such a model, researchers at the University of Bath have now investigated the effects of changes in the angiogenin (ANG) gene. It is associated with diseases that commonly occur with aging, including frontotemporal dementia, motor neuron disease and Parkinson's disease. In previous work, Vasanta Subramanian's team had already discovered that ANG has a protective effect on nerve cells if the gene is intact. In contrast, the mutated form of the gene causes nerve cells to be more vulnerable to stress, leading to premature cell death.
In their recent research, Subramanian and her colleagues examined how the mutated ANG gene affects brain development. To do this, they grew brain organoids from stem cells with and without this mutation. ANG was shown to play an important role in the speed at which stem cells develop into nerve cells. In its mutated form, the gene causes the stem cells to remain in their undifferentiated state for longer. This slowing leads to noticeable defects in the nerve cells and can then lead to illnesses later in life, as the team reports.
For the researchers, this means above all a step in the right direction towards the early treatment of age-related diseases. “I envision a time when we identify people susceptible to these diseases, screen them for genetic mutations, and offer early gene therapy to correct the defects,” says Subramanian.