Recipient: Professor David Pow
Professor David Pow is a Professor at the University of Queensland Centre for Clinical Research. He was awarded the MND and Me Foundation Research Grant for 2017.
Controlling our excitable brains …
When we talk about motor neurone disease (MND) we tend to think about death of the nerve cells in our spinal cords that connect to our muscles. However there are many more cells involved, including the nerve cells in our brains in an area called motor cortex.
We believe that one of the things that goes wrong in our brains, and which may lead to MND, is a local abnormality in the control of glutamate in our brains and spinal cords. Glutamate is a small amino acid that is abundant in our brains. It is normally tightly controlled by our brains because it is a potent “excitatory” neurotransmitter and if it becomes unregulated for any reason then cell death can occur.
We have been investigating a novel protein called EAAT5, which we discovered in both brain tissues and in the spinal cord. EAAT5 acts both as a glutamate transporter (removing glutamate from places where it acts as a neurotransmitter) and as an “off” switch to neurotransmission. Basically it is a molecular switch that inhibits the release of glutamate from nerve cells.
In our initial experiments we looked at an animal model of motor neurone disease in animals with a mutation of the SOD1 gene. While this is only a model for some inherited forms of MND, our data was exciting in that we were able to show major losses of this protein at very early stages in the disease process. Losses of this protein would, we believe, lead to the motor neurons becoming over excited due to elevated levels of glutamate, an event that would likely result in the death of these cells.
While this discovery is exciting, we all know (to misquote John Steinbeck) that “Mice are not Men”, so we have now moved our studies to an examination of human brains.
We have been excited to gain access to brain tissues from deceased donors who have either had no neurological abnormalities, or who have had motor neurone disease. This very rare resource is enabling us to look at the expression of EAAT5 in humans, and to determine if the levels of the protein, or the messenger RNA that codes for the protein, are abnormal in people with MND.
This is for us, an important journey. Joining the dots between what happens in a mouse model and what actually happens in human beings is an essential part of the translational process.
We look forward to keeping you informed as we progress on this journey.