by Mihai Ionescu
Symposium 2 at EAN 2024, the joint session co-hosted by the EAN and the Movement Disorder Society European Section (MDS), took place in a packed room on the morning of the first day of the congress, showing the growing and active interest in the field of movement disorders and particularly Parkinson’s disease.
The overarching theme of this session was related to the transition from a clinical definition of Parkinson’s disease to a biological definition and classification of the disease considering the clear picture at this point that the preclinical phase of the disease starts years before clinical onset and disease modifying therapies must be targeted to this subset of patients. Their identification and classification thus must rely on a new definition of Parkinson’s disease based on biology and not just clinical signs.
This biological definition relies on a three-component system: ‘G-S-N’, which was extensively defined in the following talks.
The session started with Dr Christine Klein, the Director of the Institute of Neurogenetics in Lubeck, Germany, approaching the genetic status of Parkinson’s disease and explaining the current knowledge and limitations in the complex field of Parkinson’s disease genetics from classic monogenic mutations to genetic risk factors, gene penetrance, mutation specific clinical features and ongoing clinical trials in gene-targeted therapies, and how all of this fits into the larger three-component system.
Dr Laura Parkkinen, the Director of the Oxford Brain Bank, held a beautiful talk on the ‘S’ (alpha-synuclein pathology) component of the biological definition, detailing the current knowledge of alpha-synuclein and Lewy body pathology in Parkinson’s disease starting from Braak’s classical staging of pathology in the central nervous system and the peripheral onset of alpha-synuclein with prion-like propagation, as well as the detection protocols of alpha-synuclein from blood, CSF, saliva, skin and GI tract derived samples. A large proportion of the talk was later dedicated to the popular subject of alpha-synuclein seed amplification assay, and its current diagnostic value for research purposes, as well as issues and limitations which must be addressed before being adopted as a clinical diagnostic tool.
Dr Jean-Christophe Corvol of the Pitie-Salpetriere Hospital and Paris Brain Institute held the lecture on the ‘N’ (Neurodegeneration) component of the Parkinson’s disease definition, covering the subjects from why there is a need for such a definition of the disease starting from the neurodegeneration viewpoint, such as the currently limited only-for-research-purposes prodromal criteria for Parkinson’s to an engaging description of the current imaging biomarkers used for central nervous system dopaminergic terminal degeneration such as DAT scan, VMAT2 binding imaging, and FDG-PET, as well as methods of substantia nigra imaging such as iron-sensitive imaging, neuromelanin sensitive imaging and free water diffusion imaging and each of their strengths and weaknesses. For the peripheral autonomic system neurodegeneration component, MIBG scanning was explained and the argument to be made for a dual nuclear imaging algorithm, as well as more novel but currently unvalidated neurotransmitter imaging methods used for Parkinson’s, such as serotoninergic and cholinergic system imaging.
The session was ended by Dr Gunter Hoglinger, Professor at the Munich Center for Neurosciences, on why this new biological definition was a necessary change from the previously pure clinical definition of Parkinson’s disease. The seminal work on the three-component ‘Syn-Neur-Ge’ system was explained and the background of each component detailed in the previous talks was reiterated with explanation of the current proposed research classification definitions in biomarker-positive individuals using each ‘G-S-N’ component, including how clinical manifestations fit into this new biological classification system.
In summary this session was an extremely detailed and passionate explanation of the novel ‘Syn-Neur-Ge’ biological classification system for Parkinson’s disease as this is a novel framework for future clinical trials in targeted disease modifying therapies of Parkinson’s disease, opening the doors for real hope in stopping disease progression in the many patients we each treat every day suffering from Parkinson’s disease.
