- Genetic changes occur when there are alterations to the DNA, some of which can contribute to the development or worsening of diseases.
- MS Australia-funded researchers studied brain tissue donated through the MS Australia Brain Bank to identify the number and pattern of genetic changes in neurons (nerve cells).
- The researchers found that from around the age of 40, neurons in MS brain lesions accumulate genetic changes more rapidly than those in normal appearing MS tissue and brain tissue from people without MS, with certain genetic changes being more common in MS lesions.
- The research suggests that chronic inflammation causes genetic changes in neurons that contribute to nerve damage and disease progression in MS.
Genetic changes – what are they and why are they important in MS?
Genetic changes occur when there are alterations to DNA in the cells of the body. When these changes occur in genes which are important for a cell’s function or survival they can contribute to the development of diseases.
Over 200 genetic changes have been linked to the development of MS. These are inherited genetic changes, which are present from birth and may increase a person’s risk of developing MS. However, genetic changes also occur naturally in cells after birth due to normal biological processes, environmental factors or disease processes. These genetic changes are referred to as somatic mutations.
Unlike inherited genetic changes, somatic mutations are not passed down from parents but instead might develop in response to inflammation and other cellular stressors. This could contribute to disease progression, particularly in progressive MS, where ongoing damage to neurons (nerve cells) plays a key role.
What did the researchers do?
Applying innovative laboratory techniques, MS Australia-funded researcher Associate Professor Justin Rubio and his team studied somatic mutations in the brain tissue of people with MS donated through the MS Australia Brain Bank and UK MS and Parkinson’s Tissue Bank. The researchers also analysed brain tissue from 16 people without MS.
The researchers looked at brain areas with older MS lesions (regions of chronic inflammation) and areas without lesions, comparing the number and patterns of somatic mutations in their neurons.
What did the researchers find?
Published in Nature Neuroscience, the researchers found the rate at which somatic mutations accumulate is two-and-half times faster in neurons located in chronic MS lesions compared to those in normal appearing MS tissue and tissue from people without MS. This accelerated rate of mutation in neurons occurred from around 40 years of age. Additionally, neurons in normal-appearing MS tissue had significantly more genetic changes than those in the brain tissue of people without MS.
The researchers also found distinct patterns of somatic mutations in neurons within MS lesions compared to normal-appearing MS tissue and tissue from people without MS, which suggests that chronic inflammation in MS is associated with specific processes that may contribute to nerve damage (neurodegeneration) and disease progression.
Why is this important for people with MS?
These findings indicate that, beyond being an immune-mediated disease, processes involved in MS also damage neurons at the genetic level. This research shows that inflammation in MS can lead to genetic changes in neurons, which may contribute to disease progression.
While further research is needed, these insights bring us closer to understanding how inflammation drives genetic changes in neurons. This could help in developing treatments that protect nerve cells and support their repair, particularly in progressive MS, where ongoing damage to neurons plays a major role.
Associate Professor Justin Rubio said, “Our work identifies a previously unknown mechanism that may cause neurons to get sick and die as MS progresses. This discovery is not a treatment, but a clue to a process that could be targeted by new treatments. Learning more about the processes involved in causing the accelerated mutation rate in neurons in lesions is a first step towards developing new treatments for progressive MS.”
“We are extremely grateful to donors to the MS Australia Brain Bank and their family members for making this work possible, and to MS Australia for contributing to the funding of this project”.
For more information about the MS Australia Brain Bank, please click here.
