The morning session
The morning sessions began with a talk by Dr Michel Goedert (MRC Laboratory of Molecular Biology at Cambridge) and Dr Tim Bartels (UK Dementia Research Institute at UCL, UCL Queen Square Institute of Neurology), discussing alpha-synuclein structures in human brain and MSA.
Using cryo-electron microscopy Dr Goedert and his team showed that α-synuclein inclusions from the brains of individuals with MSA are made of two types of filaments, each of which consists of two different protofilaments. In each type of filament, non-proteinaceous molecules are present at the interface of the two protofilaments further demonstrating that α-synuclein filaments from the brains of individuals with MSA differ from those of individuals with other parkinsonian conditions, which suggests that distinct conformers or strains characterize MSA.
Dr Bartels talked about the structure – function relationships in synucleinopathies. He showed how different disease strains have different biological activities and furthermore, that the activity of alpha-synuclein strains depend on the brain region that is involved in the disease. Finally, he introduced the topic of research into the origin of strain diversity.
This was then followed by a session on the genetics of MSA chaired by Professor Henry Houlden (Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology) and other researchers from UCL discussing findings on somatic structural variants in MSA (Professor Christos Proukakis, Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology), brain DNA methylation in MSA (Dr Conceicao Bettencourt, Queen Square Brain Bank, UCL Queen Square Institute of Neurology) and dissecting the SNCA locus with long-read RNA-sequencing to understand synuclein disorders (Dr Mina Ryten, UCL GOS Institute of Child Health).
The final session before lunch was chaired by Professor Anette Schrag (Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology) and covered updates on biomarkers where the panel discussed established biomarkers that predict neurodegeneration and progression in MSA (Dr Viorica Chelban, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology), ongoing efforts develop early diagnostic tests for MSA using multiple blood-based biomarkers (Farid Khan, CEO Pharmakure) and advanced anatomical MRI for parkinsonian disorders including MSA (Dr Christian Lambert, Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology).
Image: Samantha Pavey and Dr Viorica Chelban
Afternoon session
The Research Symposium afternoon was split into two sessions; Towards Improving Diagnosis and Prognosis of MSA and New Horizons in MSA Drug Trials.
In the first session Professor Jalesh Panicker (UCL Queen Square Institute of Neurology) talked about the latest diagnostic criteria for MSA and how the criteria will support improved diagnostic accuracy and earlier diagnosis for people with MSA.
Dr Valeria Iodice (UCL Queen Square Institute of Neurology) then spoke about autonomic features of MSA, and whether autonomic biomarkers would be helpful to aid early diagnosis. Autonomic features include bladder issues, fainting, constipation, and sleep disorders. Dr Iodice’s team have looked at how autonomic tests may be able to act as a ‘biomarker’ to identify people with MSA at an earlier stage – this work is ongoing.
Dr Yee Goh (Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology) then talked about the PROSPECT-M Study, which tracks people with MSA over time and is building a robust database of clinical and biobank information that acts as a research resource for studies into MSA.
Dr Christopher Kobylecki (Salford Royal NHS Foundation Trust) talked about the use of PEG – a feeding tube – in people with MSA, including what evidence and clinical guidance there already is for PEG use and what would be useful to know in future.
The second session focussed on clinical trials. Professor Huw Morris (Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology), introduced the Horizon Phase I trial which will look at feasibility and safety of using antisense therapy in people with MSA. An antisense therapy binds with RNA, halting the process of creating a disease-causing protein at a genetic level. If shown to be safe, this could lead to further trials to examine if such therapy could have an effect on the progression of MSA.
David Stamler MD, CEO Alterity Therapeutics, presented information from Alterity Therapeutic’s Phase II trial of a compound called ATH434, which is being tested to see if it affects levels of iron accumulation in the brain.
Professor Tom Foltynie (Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology) shared an update on the phase II study of Exenatide. Exenatide is a GLP-1 receptor agonist used in the treatment of diabetes and is being tested in people with MSA to see if it has any effect on the progression of MSA.
The day finished with Dr Iodici sharing data from a study of a medication called Ampreloxetine which can improve symptoms of postural hypotension.
The day was a great success, allowing researchers the opportunity to share their findings, network with colleagues and harness shared enthusiasm and momentum for research into MSA.
"The networking component was particularly valuable for my research team in that we are just starting to work on an MSA Trust funded project and this allowed us to establish useful connections with other groups.""I have left with much more information on diagnosis, management and general care for people with MSA and with new ideas for research and collaborations on this condition."
Image: Professor Jalesh Panicker, Dr Valeria Iodice and Dr Christian Lambert.