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Stem Cell Models: Non-animal research into neurodegenerative diseases

Researcher: Dr Jade Edey

Location: FRAME Lab, University of Nottingham

Inflammation of cells in the brain is associated with the development and progression of degenerative brain diseases such as Alzheimer’s and Parkinson’s. Former FRAME Lab PhD student Jade developed human cell models to study the role of specific proteins in these inflammatory processes. These models have the potential to replace the use of rats, mice, and other animals in neurodegenerative disease research.

The problem

Parkinson’s disease affects over 10 million individuals worldwide with diagnosis rates rising. It’s characterised by a loss of brain cells, called neurons, that produce dopamine. Dopamine is a neurotransmitter, a chemical which sends messages between brain cells. Alarmingly, noticeable symptoms, such as tremors, only emerge after 60% of these vital brain cells have been destroyed. The precise mechanisms behind this brain cell degeneration remain poorly understood, despite years of research, including many experiments using animals. The condition is approximated in animals through gene editing or administering of toxic chemicals to cause brain cell damage and loss.

In 2022 over 198,800 procedures were carried out on animals for research into the nervous system and just over 45,500 more for research into human nervous system and mental disorders.

The human immune system differs greatly from that of rodents, therefore findings from inflammation studies in rodent models are not always applicable to humans.

Dr Jade Edey

The project

Jade’s project focused on a protein called Nurr1 which helps control to what extent genes are ‘switched’ on or off in a cell. Nurr1 is essential for the development, maintenance, and survival of dopamine-producing neurons. It also has a potential role in regulating inflammation of brain cells, through a process called SUMOylation. This is where a protein known as a SUMO protein is added to another protein, such as Nurr1, modifying it by changing its structure and function. This is a reversible process. SUMOylation tags proteins for the cell to remove or destroy, and guides relocation of proteins within the cell.

Due to the changing nature of SUMOylation it can be a challenging process to research and understand. To study the role of SUMOylation, Jade required a source of human-relevant brain cells, so she focused on stem cells sourced from human blood. These cells have the potential to give rise to any type of body cell, including neurons or microglia, which are immune cells within the brain.

The potential

Nearly 200,00 procedures were conducted on animals in 2022 for basic research into the nervous system, and almost 50,000 more for studying the human nervous system and mental disorders. Jade’s pioneering work at the lab generating a sustainable source of human neurons and microglia will help accelerate these time and resource intensive techniques to make them more efficient and accessible in the future.

Human-relevant models like these can not only advance research into devastating conditions like Parkinson’s disease, but also help end the use of thousands of animals in this field of research. The limitations of using animals to study human conditions include differences in our physiology, And more human-relevant approaches could provide much more insight into the underlying mechanisms of increasingly common, and devastating conditions such as Parkinson’s, allowing earlier detection and more effective treatments.

Dr Jade Edey Completed her PhD research at the FRAME Lab in 2023

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