When our core body temperature is cooled, our bodies switch on a protective response called the ‘cold stress response’ which prevents damage to our nervous system by slowing metabolism and protecting cell structures. This response is activated in mammals that hibernate in winter and in people who undergo therapeutic cooling in hospital following stroke or spinal cord injuries. The cold stress response is also activated in people who do ice bathing and cold-water swimming, which has been gaining more attention due to its reported positive effects on mental health and general well-being. What if there was a way we could harness the positive effects of the cold stress response as a treatment for MND?
The Bill Gole Postdoctoral Research Fellowship is awarded to an early career researcher in MND to kickstart their research career and provide funding towards project costs. In 2024, I was awarded this fellowship to further investigate this question. Currently, pharmacological treatments for MND are targeted at singular disease processes. However, we are learning more all the time how MND is a complex disease involving the culmination of a range of different disease processes which lead to the symptoms of disease. An important step in effectively treating MND will be the ability to act on a range of these pathways at the same time.
This is where we believe that our project comes in. One way that the body achieves protection during cold stress is to increase the amount of a molecule known as RBM3. Previous evidence has shown that increased RBM3 following cooling has a range of positive effects including protection against loss of nerve cells, stop muscles from wasting and decrease inflammation. The ability to halt these processes is very relevant in MND. However, cooling the body can have adverse effects such as the shivering response, and getting into an ice bath may not be an option for everyone.
Recently, our colleagues in Europe developed a drug that could increase the levels of RBM3 without the need for cooling, and this has been successful in reducing detrimental changes in other brain diseases. To begin to understand whether this drug is effective in MND, we will first work study its effects in the commonly used mSOD1 mouse model of MND, which displays many of the core disease features of MND and by first carrying out our experiments in mice we will be able to understand complex biological processes in a living system.
The provision of the Bill Gole Fellowship will allow us to firstly determine whether the RBM3 drug is able to slow disease progression and protect against MND-related changes. Secondly, we will also further investigate the effects of whole-body cooling and whether this more non-pharmacological approach can be effective in altering disease trajectory in MND. The combination of these two studies will allow us to learn more about the therapeutic potential of cold stress in MND.
If you would like to know more about the project please feel free to contact me: Rachel.Atkinson@utas.edu.au
