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7 months ago

MSWA Bulletin Magazine Summer 2022

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Keeping your cool this summer | Welcome Melanie Kiely CEO | MSWA Stationary Cycle results | Pain and pain management series: Part 3

Professor Orla Hardiman,

Professor Orla Hardiman, Professor of Neurology and a world leader in MND research said: “This is a very important and exciting body of work. A major barrier to providing the right drug for the right patient in MND is the heterogeneity of the disease. This breakthrough research has shown that it is possible to use patterns of brain network dysfunction to identify subgroups of patients that cannot be distinguished by clinical examination. The implications of this work are enormous, as we will have new and reliable ways to segregate patients based on what is really happening within the nervous system in MND.” FROM HD BUZZ Read more at: ‘Seeing’ the toxic huntingtin protein in people with HD; Dr Rachel Harding, December 08, 2021. Scientists have developed a tool which allows us to ‘see’ toxic clumps of the huntingtin protein using special scanners. People with Huntington’s disease (HD) make a toxic form of the huntingtin protein which forms clumps in cells of their bodies, which accumulate during HD progression. Tracking how these clumps form over time, or how they change when people with HD take different treatments, could help us better understand the progression of HD and which medicines help patients most. We all have 2 copies of the huntingtin gene but for people with HD, one of their copies has a type of mutation called a repeat expansion. This mutation occurs in a repetitive bit of the huntingtin gene DNA code which has the letters “C”, “A” and “G” repeating over and over. If you don’t have HD, you will have less than ~35 CAG repeats in your huntingtin gene but for people with HD, the mutation means they will have more than 35 CAG repeats in one of their huntingtin genes. Scientists from labs across the UK, Germany, Italy, Sweden, and the US have developed molecular tools which allow us to ‘see’ these clumps in living animals, and hopefully soon, HD patients. These tools bind to the huntingtin protein clumps and have chemical decorations, called radiolabels, which mean that they light up when looked at by PET (positron emission tomography) scan. Making PET tracers which allow researchers to see the toxic clumps of huntingtin protein is attractive for several reasons. Firstly, a PET scan can be performed on patients at multiple time points throughout their life so we can track how the clumps accumulate over time throughout the progression of HD. Many of our current methods for looking at huntingtin clumps in a patient’s brain can only currently be done at the very end of the disease on post-mortem tissue. Secondly, PET scans are non-invasive and allow us to look right in the brain whereas more intrusive procedures like measuring huntingtin protein in spinal fluid provide only a proxy for what we think is happening in the brain. Thirdly, the clumps are formed from the toxic form of the huntingtin protein so PET scans will allow researchers to specifically measure changes to this specific form of mutant huntingtin. A clinical trial is being conducted called iMagemHTT study, which will investigate the huntingtin tracer in people. The trial will use PET/ MRI imaging to understand how the PET ligand tracks huntingtin in the brain. The amount of huntingtin clumps in the brains of people with HD is a good biomarker of disease progression. Biomarkers are objective measurements scientists and clinicians can take to track HD’s progression which can be important for working out the best treatment options, as well as if treatments are working properly. It is possible that HD patients in the future might be monitored by PET scan using these types of tools. If the PET ligands work as scientists hope, it could also be used to track huntingtin-lowering in the brain in future trials. Despite setbacks, huntingtin lowering is still a promising strategy for treating HD and is being pursued by several groups, all have clinical trials under way. Regardless of what happens with Huntingtin lowering, these exciting new tools are giving scientists the ability – for the first time ever – to track mutant Huntingtin protein across the entire brain of living HD patients, which is a huge advance. 12