20 Years of alpha-synuclein in Parkinson’s disease and related synucleiopathies: from the bedside to the bench and back to the patient
Janice Holton, Director of Neuropathology, Queen Square Brain Bank, UCL Institute of Neurology, London, UK
Athens, Vravrona: I was fortunate to participate in this excellent meeting held in an idyllic location on the coast near Athens, Greece. The local organising committee, led by Professors Leonidas Stefanis and Kostas Vekrellis, created a fascinating programme attracting speakers and researchers from around the world. The relaxed and friendly atmosphere allowed participants with different skills and perspectives to interact, learn from each other and develop collaborations.
The programme commenced with a clinical workshop at which a series of interesting clinical cases were presented for discussion, some having the benefit of a neuropathological diagnosis. This led to a lively exchange of ideas and was a great learning experience for the audience, which included a number of young clinicians. This was complemented by the subsequent talk presenting the state of the art current treatment strategies for Parkinson’s disease (PD). The first day culminated in a fantastic presentation by Professor Fahn who led us through the intriguing story of the development of treatments for PD leading to the introduction of dopamine therapy 50 years ago, thus revolutionising the treatment of PD and providing huge benefit to the lives of patients.
At the heart of the meeting was the recognition 20 years ago that mutation in SNCA, the gene encoding alpha-synuclein, was the cause of inherited PD in families originating from the village of Contursi in Italy. The story of how this mutation was disseminated from Greece to Italy in ancient times was elegantly presented by Professor Barone. The discovery of a mutation in SNCA, together with the subsequent demonstration that alpha-synuclein is a major component of Lewy bodies, the neuronal inclusions that characterise PD pathology, and also the cellular inclusions in multiple system atrophy (MSA), has been of crucial importance in our current understanding of these diseases. We were treated to a marvellous talk by Professor Spillantini who described how alpha-synuclein was first recognised in Lewy bodies by herself and colleagues in Cambridge. Professor Hardy provided an overview of the genetics of PD, discussing additional mutations in SNCA and the many other genetic discoveries that have been made in the past 20 years that provide insight into genetic risk and disease mechanisms in PD.
The scientific sessions and poster presentations catered to the wide range of participants by covering many topics relating to clinical and neurobiological aspects of alpha-synucleinopathies including the presentation of original work. The structure of the meeting included a round table discussion at the end of each scientific session providing a lively forum for discussion between speakers and the audience. Topics covered included sporadic and genetically linked forms of PD associated with mutations in SNCA, LRRK2 and GBA. Dementia with Lewy bodies and sleep behaviour disorders were also discussed in detail.
A session devoted to MSA was very well attended and prompted lively discussion. The presentations covered clinical aspects, including an in depth discussion of the difficulties of diagnosis presented by Dr Stamelou. The neuropathology of this rare condition was described including presentation of the insights that neuropathological studies provide into the mechanisms of disease. In further talks the contributions of cell biology and animal models to understanding MSA were clearly outlined. Many of the presentations relating to the neurobiology of alpha-synucleinopathies had direct relevance for the understanding of MSA. Presentations addressing the cellular function of alpha-synuclein, protein degradation and clearance, protein aggregation and the interesting concept of the spread of pathology within the brain were considered in detail by many speakers. We were privileged to hear from experts in all of these fields and to gain insight into the current research aiming to enhance our understanding of disease mechanisms in alpha-synucleinopathies, including MSA, with the purpose of developing disease modifying therapies. In the final session of the meeting it was exciting to hear reports from representatives of pharmaceutical companies regarding new treatments entering clinical trials.
This wide-ranging meeting was stimulating for all involved in investigating MSA and PD bringing together the wide community of researchers in all clinical and scientific aspects of these diseases. The involvement and support of organisations including the MSA Coalition was widely acknowledged and appreciated. I look forward to the opportunity of participating in the next meeting two years from now and I am confident that much progress will have been made.