Following the mid-morning break, which was filled with the smell of freshly brewed coffee, we attended a session on biomarkers. Biomarkers are measurable indicators of biological changes that can confirm the presence of disease and be used to monitor disease progression or response to drug treatments. Read more about biomarkers here. Seven talks in this session each focused on different MND biomarkers.
Dr Rachael Dunlop, who’s based at Brain Chemistry labs in the US, studied using microRNAs from the blood to diagnose MND. MicroRNAs are small fragments of RNA that can help to control which genes are made into proteins in our cells. Dr Dunlop and colleagues had previously identified a unique ‘signature’ of 8 microRNAs that could be measured from processed blood samples and used to determine whether someone had MND. However, the processes required were time consuming, costly and needed lots of expertise, which limits how useful the technique could be for widespread use.
So the researchers focused on improving the process. Their streamlined method measures microRNAs directly from unprocessed blood and can accurately identify MND samples from healthy samples more than 98% of the time. The researchers are now exploring how well the test is able to differentiate MND from other neurological diseases. This shows promise for improved diagnosis of MND.
Dr Robert Bowser, a researcher based at the Barrow Neurological Institute and nVector Inc in the US, has been exploring biomarkers in cerebrospinal fluid (CSF), the fluid surrounding cells in the brain and spinal cord. Calpain-2 is a protein linked to nerve cell damage, and it is increased in people with MND. Dr Bowser explained that his team have identified biomarkers for calpain-2 activity in the CSF. These biomarkers appear to rise when calpain-2 is active, and people with MND have higher amounts of these proteins in their CSF.
A company called Amylyx have developed a treatment called AMX0114, which prevents calpain-2 from being made. Dr Bowser explained that they are measuring the effects of AMX0114 by looking at the levels of the biomarkers in the CSF which rise when calpain-2 is active. The research is still in its early stages, but it shows promise for using these proteins as markers of nerve damage and to track how well AMX0114 is hitting its target in studies exploring the potential therapeutic benefits of the drug in people with MND.
To conclude the biomarker session, Dr Katie Hanna shared an update on her work in the lab of Prof Jenna Gregory at the University of Aberdeen, which is funded by the MND Association. Interestingly, our skin has the same origin as neuronal tissue in growing embryos, which means some of the characteristics are shared between these two types of tissues. We already know biomarker changes in the skin can occur before the onset of neurological symptoms of MND. Katie discussed the potential of detecting TDP-43 pathology in skin cells as a pre-symptomatic biomarker of MND. The researchers studied skin samples from 17 people who were pre-symptomatic then developed MND. They measured TDP-43 clumps in the samples and found sweat glands in the shoulder and back had the highest amount of abnormal TDP-43 biomarker. This study shows that skin tissue, as a minimally invasive source of biomarkers, likely has a lot of potential for pre-symptomatic biomarker development in the future.
