by Isabella Colonna
This Symposium on Early detection and treatment of Parkinson’s disease was organised in co-operation with the International Parkinson and Movement Disorder Society – European Section and was moderated by Prof. Carlo Colosimo and Prof. Tiago Fleming Outerio.
The first lecture, Imaging -based diagnosis of pre-motor parkinsonism, presented by Prof. Nicola Pavese, focused on imaging biomarkers of prodromal phases of Parkinson’s disease (PD). It has been shown that neurodegeneration and neuronal loss start very early in PD. The identification of biomarkers able to identify PD in its early stages might be helpful to understand the right point in time when disease-modifying therapies should be started. In this context, neuroimaging may play an important role to elucidate early pathological changes. Studies using molecular imaging techniques described an early involvement of the nigrostriatal pathway, decreased acetylcholinesterase density in peripheral organs, loss of cortical cholinergic function as well as increased activated microglia in prodromal PD. Furthermore, pre-motor stages of PD were found to present reduced intensity of the substantia nigra at the neuromelanin MRI and midbrain hyperechogenicity on transcranial ultrasound.
The second lecture of the session, titled ‘Biological versus clinical diagnosis of PD’, was held by Prof. Outerio. He emphasised that the accuracy of clinical diagnosis of PD is not yet satisfying and did not improve in the last 25 years; thus, biomarkers are urgently needed. PD is not just a motor condition since non-motor features and dementia may occur at any time during the course of the disease. Several possible pathogenic mechanisms underlying neurodegeneration in PD have been identified, such as genetic mutations, neuroinflammation, and mitochondrial dysfunction. Furthermore, the aggregation of pathological proteins plays a central role in PD and in neurodegenerative disorders, leading to a loss of normal function and to a gain of toxic function. Outerio concluded by underlining the urgent need to define biomarker-based diagnostic criteria for PD.
In the last lecture Prof. Angelo Antonini gave an update of disease modifying treatments in PD. He talked about new therapeutic approaches that are currently under investigation. Small molecule-based colloidal nanoparticles have been developed to inhibit pathological protein aggregation. Among these, UCB0599 is a brain-penetrant small-molecule inhibitor of alpha-synuclein misfolding and is currently under investigation for the potential to slow the progression of PD. Furthermore, novel engineered nanobodies specific for N-terminal regions of alpha-synuclein have been shown to be able to recognise Lewy-Body pathology and inhibit in-vitro seeded aggregation and toxicity. In the last years much effort has been made to develop antibodies targeting alpha-synuclein. Among these, Prasinezumab, which is currently in phase II, has been shown to slow motor progression. Furthermore, specific active immunotherapy with PD01A, peptide targeted against oligomeric α-synuclein, has recently been shown to be safe and well tolerated in phase 1 trial.
In conclusion, this session gave an important insight into pathological changes underlying PD and on imaging markers that may play an important role in the detection of prodromal PD, emphasising the urgent need to define biomarker-based diagnosis of PD and to promote further research on new MRI and PET techniques. Moreover, this session gave an important overview of potential therapeutic agents for PD which are currently under development and investigation.