Grant winner 2016
Grant type: Pilot grant
Principal investigator: Professor Liam Gray
Institution: Cardiff University
Duration: 24 months
Scientific title: Is interneuron transplantation feasible in human Temporal Lobe Epilepsy?
“This is an exciting project that will give significant insights into the feasibility of cell transplantation for treating seizures and cognitive problems in patients with temporal lobe epilepsy.” Professor Liam Gray (pictured)
A loss/dysfunction of inhibitory neurons known as interneurons in the hippocampus of the brain is one of the earliest changes in temporal lobe epilepsy (TLE), and it is central to the imbalance in excitation/inhibition that underlies the condition.
In theory, it should be possible to address this balance by replacing these lost/damaged interneurons with new ones, and experimental attempts to do this have been promising. Researchers have successfully transplanted human stem cells that generate interneurons into the brains of epileptic mice, and they have seen a 90% reduction in seizures.
However, the animals used in these studies did not have active immune systems, which was integral to making sure they did not reject the transplanted cells. In human TLE the hippocampus is very inflamed, and long-term suppression of the immune system is not feasible.
If this is to become a realistic treatment for TLE, researchers must understand what signals are exchanged between the inflamed hippocampus and transplanted cells in humans, and how this affect the survival, development and integration of the new interneurons. Only with this knowledge will they be able to provide an optimal environment for transplanted cells and the best chance of success.
A 3D cell culture is an artificially-created environment, in which biological cells are permitted to grow or interact with their surroundings in all three dimensions. It is a very useful tool for studying the function and interactions of different cells/tissues in health and disease. Professor Gray and colleagues have recently mastered the development of 3D cultures of human epileptic brain tissue that has been removed during epilepsy surgery. These cultures survive healthily for 6-8 weeks and exhibit all the hallmarks of inflammation seen in TLE. The team has added human stem cells to these cultures, and has found that, although many die, some survive and show signs of early maturation.
During this grant the group will use their cultures to try and find out what it is that allows the transplanted cells that survive and develop to do so.
The knowledge gained from this study will be vital to the progress of this treatment to human clinical trials of TLE, which Professor Gray envisages could potentially be in the next 3-5 years.
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