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Multiple Sclerosis (MS) is a neurodegenerative disease with no clear cause and no cure. To improve the lives of people with MS, treatments must stop the disease from progressing, protect nerve cells in the brain, and restore brain function.
Myelin is the insulating sheath that wraps around nerve cells in the brain. In MS, the cells that produce the myelin die, leading to myelin loss in the brain. Myelin loss slows or stops nerve cells from sending the electrical signals that they use to communicate in networks within the brain. Currently, it is not known how myelin loss then leads to the death of underlying nerve cells and worsening symptoms in people with MS over time.
However, Dr Kalina Makowiecki and her team suspect that myelin loss is not only associated with slowing of the electrical signal, but with other changes to nerve cell communication which causes them to respond more strongly to chemical signals. When this response goes too far, nerve cells can die, leading to disease progression.
This project aims to understand how nerve cell communication changes, starting from the earliest stages of myelin loss, and how this could lead to the death of nerve cells. The project also aims to identify how treatments could target nerve cell communication to protect nerve cells, halt disease progression and restore brain function to overcome debilitating symptoms in people living with MS.
Dr Makowiecki and her team have made excellent progress on this project. They have demonstrated that myelin loss affects the communication between nerve cells in the brain of laboratory models of MS. The team’s findings indicate that myelin loss not only slows down the communication between nerve cells but also affects the structure of these cells and their connections, affecting how reliably one nerve cell responds to another.
Their research has also demonstrated that myelin loss disrupts the delicate balance between “excitatory” (go) signals and “inhibitory” (stop) signals in the brain. Specifically, laboratory models of MS had a decreased response to excitatory signals and increased response to inhibitory signals. This was found to occur rapidly after myelin loss and may contribute to some of the symptoms in MS, such as memory and concentration problems, as well as depression and anxiety related symptoms. This is a promising finding that will be investigated further as part of the project.
Interestingly, the team has discovered that myelin repair can reverse the changes to the structure of nerve cells caused by myelin loss. This discovery holds great promise, as it suggests that treatments that target myelin repair are likely to be an appropriate intervention to potentially reverse symptoms of MS.
Moving forward, Dr Makowiecki and her team will continue to investigate how MS, particularly myelin loss, affects nerve cell communication. Understanding this will hopefully pave the way towards identifying and developing treatments that prevent disease progression.
Dr Makowiecki has presented this work at national and international conferences and is preparing several manuscripts for publication in scientific peer-reviewed journals.
Updated 31 March 2023
Dr Kalina Makowiecki
$428,231
2022
3 years
Current project
