On June 21st, 2024, the Parkinson’s Disease Centre of Excellence at King’s College Hospital and Kings College London (KCL) hosted a scientific symposium to discuss the latest advancements in Parkinson’s disease (PD) care and research, identify existing gaps in care, and encourage international collaboration. The event featured leading PD experts from around the world, who shared their latest findings and insights into present advancements.  

The sessions were chaired by Professor Peter Jenner (KCL), Professor Huw Morris (University College London, UCL), Professor Pablo Martinez-Martin (Consortium for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain), Professor Anette Schrag (UCL), Professor Cristian Falup-Pecurariu (Transilvania University), Dr. Vinod Metta (KCL), Dr. C Padmakumar (John Hunter Hospital, Australia) and Professor Per Odin (Lund University).

Professor K. Ray Chaudhuri, Director of the Parkinson’s Disease Centre of Excellence at KCL, and Sir Nicholas Mostyn, Co-Founder of the ‘Movers and Shakers’ podcast, which focuses on life with PD, introduced the event. Together, they recently founded the King’s Parkinson’s Charity, aiming to bridge gaps in PD research and tackle inequalities in care. They discussed the concept of PD being an “Iceberg”, whereby many non-motor symptoms remain submerged and unnoticed. To address this, they developed a “Dashboard” designed to highlight gaps in care by encompassing non-motor and motor symptoms as well as overall lifestyle-related care (Qamar et al., 2023). In their opening remarks, they highlighted the ongoing challenges faced by individuals with PD and emphasised the urgent need for collaborative efforts to accelerate solutions. 

Professor Nobutaka Hattori of Juntendo University, Tokyo, delivered the first lecture, addressing the relationship genetic variants and neuropathological states which symbiotically explain the progression and manifestation of PD. One example being the finding that variants of the PRKN gene lead to a disruption of mitochondrial quality control, resulting in increased cell fragility. Furthermore, Professor Hattori discussed the overlap between pathological mechanisms and different PD-causing variants, presenting the conflicting explanations, which prevent a singular, definitive narrative of PD’s pathology from emerging. For instance, non-autonomous cell death has been identified as a common pathway among PRKN and LRRK2 carriers with PD. Despite these complexities, Professor Hattori highlighted that the diverse spectrum of pathological states associated with PD can be leveraged through personalised medicine, offering optimism for developing targeted treatments tailored to individual patients. 

Next, Professor Tony Schapira, UCL, tackled the fundamental question, “What is Parkinson’s disease?” He emphasized that the answer varies depending on the community asked, with varying perspectives amongst individuals living with PD, neurologists, neuropathologists and academics. Professor Schapira underscored the importance of asking the right questions, which has led to the identification of key defining features of PD, such as alpha-synuclein aggregation, disruption of the gut microbiome, and genetic and environmental influences. These findings have paved the way for the development of novel therapeutics. One key example discussed by Professor Schapira was the upcoming phase 3 Ambroxol trial, which follows promising results from the phase 2 trial, indicating the drug’s efficacy in slowing PD progression for both GB1 carriers and non-carriers.

Following this, Professor Per Svenningsson, KCL, discussed promising diagnostic biomarkers for PD. This included alpha-synuclein seed amplification (SAA) in skin biopsies, which have demonstrated high specificity and sensitivity in detecting misfolded alpha-synuclein (a-syn) in skin biopsies and cerebrospinal fluid (CSF) from individuals with PD. Professor Svenningsson emphasised two critical points when evaluating biomarkers: first, the importance of early detection of PD, and second, the ability of these biomarkers to accurately differentiate between overlapping disorders. For example, another biomarker, DOPA decarboxylase was found to distinguish between PD and Alzheimer’s disease (AD). These advancements represent significant progress in supporting the clinical diagnostic pipeline for neurological conditions.

Dr. Karolina Popławska-Domaszewicz, Poznan University of Medical Sciences and honorary researcher at Kings Parkinson’s centre, further contributed to recent findings of the genetics of PD. Dr. Popławska-Domaszewicz presented genetic mutations associated with non-motor related symptoms and discussed the extent to which these variants may guide as biomarkers of specific non-motor symptoms. This included evidence reporting that GBA1 variants are associated with hallucinations and delusions at early PD stages, TRPM8 variants linked with pain and PD, single nucleotide polymorphisms in DRD2 genes associated with ‘sleep attacks’ and COMT polymorphisms and LRRK2 mutation Y1699C, associated with pain in PD, the latter of which has been associated with unilateral leg tremors and painful foot dystonia which may need targeted treatment. 

Professor Mitul Mehta, KCL, then discussed the advancements in neuroimaging techniques and their impact on our understanding of the cognitive networks, pathophysiology, and neuroarchitecture associated with Parkinson’s disease (PD) symptomatology. He presented findings from a recent study conducted by his lab, which identified the involvement of cortical structures linked to visual hallucinations in PD, independent of those associated with cognitive decline. The study brought attention to the role of brain regions involved in attention control, extending beyond localized Lewy body pathology. These findings underscore the potential of neuroimaging techniques to clarify variation in the non-motor symptoms experienced by PD patients and to support the development of a personalised PD staging system.

Poster presentations were subsequently held during the event, chaired by Dr. C. Padmakumar, Dr. Ivana Rozenweig (KCL), Dr. Karolina Popławska-Domasiewicz, and Dr. Haider Dafsari. Ms. Aleksandra Podlewska was awarded first prize for her presentation titled “Dance Away the Parkinson Blues,” and Dr. Daniele Urso received second prize for his presentation on “Clinical Trajectories and Biomarkers for Weight Variability in Early Parkinson’s Disease.”

The symposium proceeded with Professor Keyoumars Ashkan, KCL, discussing recent advancements in deep brain stimulation (DBS). Significant developments include segmented electrodes, which require lower thresholds to achieve therapeutic effects compared to traditional leads, alongside smaller, longer lasting, and rechargeable batteries. These innovations enhance patient comfort and quality of life, promoting autonomy as patients no longer rely on others for battery recharging. Professor Ashkan highlighted streamlined DBS workflows whereby patients no longer need to leave the operating theatre, reducing the risk of mishaps and expediting the procedure. This efficiency supports better planning, facilitates teaching opportunities, and lowers overall costs. Emphasizing the importance of precision, Professor Ashkan noted that while novel innovations enhance DBS outcomes, they complement rather than replace accurate foundational methodologies. 

Dr. Haider Dafsari, Cologne University Hospital, furthered the discussion on DBS, presenting findings on the contrasting effects between ventral intermediate nucleus (VIM-DBS) and subthalamic nucleus (STN-DBS). Specifically, VIM-DBS was associated with worsening non-motor symptoms, whereas STN-DBS showed improvement. Dr. Dafsari suggested that this variability might stem from different underlying pathological processes, as exemplified in the body-first versus brain-first model. Furthermore Dr. Dafsari explained the positive effects associated with Transcutaneous auricular vagal nerve stimulation (taVNS) in improving non-motor symptoms including depression, increasing quality of life and decreasing overall non-motor burden.

Professor Per Odin, discussed advancements in levodopa delivery methods, highlighting the limitations of oral dopamine therapy. While oral medications can normalise motor function, they do not halt the progressive degeneration of the substantia nigra, associated with onset of wearing-off symptoms. Professor Odin emphasised the need for continuous levodopa delivery methods to overcome these limitations. He elaborated on how continuous delivery systems like Duodopa address issues such as poor solubility of oral levodopa. Duodopa has been shown to maintain therapeutic plasma levels throughout its infusion duration, thereby improving motor fluctuations, non-motor symptoms, and reducing caregiver burden.Professor Odin concluded his lecture by discussing Foslevodopa/Foscarbidopa, exemplifying its benefits such as stabilising sleep patterns and alleviating early morning akinesia. These advancements represent significant strides in enhancing treatment efficacy and quality of life for PD patients. 

Professor Daniel Weintraub, University of Pennsylvania School of Medicine,​ discussed the significance of neuropsychiatric symptoms in PD, available pharmacological and non-pharmacological treatments, emphasising that these symptoms are common from the onset of the disease and can worsen as the disease progresses. Results from a previous study which found that by the fifth year of the disease, over 50% of patients are diagnosed with 3 or more psychiatric disorders, were presented. Professor Weintraub explained the significant comorbidity of these symptoms, suggesting that focusing on cognitive symptoms more broadly, rather than individually, can enhance our understanding and management of PD.

Professor Dag Aarsland, KCL, discussed cognitive impairment and dementia in PD, highlighting the significant variation in the rate of cognitive decline among patients, noting that approximately 50% of PD patients develop dementia within 10 years of diagnosis, with over 80% affected after 20 years. Professor Aarsland explored the underlying pathological mechanisms contributing to Parkinson’s dementia, such as mitochondrial pathology, disruptions in the gut microbiome, genetic predispositions, and neurotransmitter dysfunction. An emphasis was placed upon recent biological staging systems of PD that consider advances in alpha-synuclein detection. These systems hold potential for understanding the heterogeneity of pathology among people with PD and accelerating treatments that can slow down and/or prevent cognitive decline.

Professor Cristian Falup-Pecurariu, presented on viral parkinsonism and theories attempting to explain the correlation between COVID-19 and PD. This included the shared cardinal symptom of hyposmia between both conditions which may lead to a misdiagnosis of COVID-19 in those with PD, along with the psychological effects of lockdown on PD patients, including lack of exercise and loneliness which can worsen symptoms. Professor Falup-Pecurariu suggested that while it is unlikely that the virus directly causes PD, it may aggravate specific motor and non-motor symptoms including bradykinesia, rigidity, dyskinesia, pain, depression, fatigue, and sleep disturbances. In response to these challenges, consensus guidelines from the European Academy of Neurology (EAN) and the Movement Disorder Society (MDS) are being developed to guide clinical care and management of neurological patients with COVID-19. 

Professor K Ray Chaudhuri concluded the event, by outlining how technological and data-driven advancements can enhance comprehensive care for individuals with PD. This includes the components of the Chaudhuri dashboard including motor and non-motor symptoms, vision health , gut and oral health, bone health and falls, along with comorbidities, co-medications and dopamine agonist side effects. Importantly, Professor Chaudhuri addressed recent disparities in care based on ethnicity, noting findings that Black and Asian individuals with PD are less likely to receive analgesics despite reporting similar pain levels to their white counterparts. Furthermore, Professor Chaudhuri discussed latest findings from this group concerning the use of the Parkinson’s Kinetigraph (PKG), a wearable sensor found to aid clinical diagnosis of early morning off in patients for whom this was previously unrecognised when using traditional clinical assessments alone. 

King’s Parkinson’s charity is currently developing comprehensive care pathways for Parkinson’s patients, spanning daily management to long-term care strategies. This initiative is supported by numerous research projects, including the “Stepped Care” programme, which integrates cutting-edge research with clinical practice. A key focus is the use of sensors in clinical settings to monitor crucial aspects of wellness in PD, such as gut health, bone health, mental health, oral health, vision, falls, mobility, and management of medications and comorbidities. The recent symposium aimed to consolidate and emphasise the importance of these parameters in Parkinson’s care, encourage a holistic approach to patient well-being. 

The symposium not only celebrated current achievements but also galvanised the global PD community toward collaborative research endeavours and patient-centred care innovations, marking a crucial step forward in the quest to improve outcomes and quality of life for individuals living with PD. 

Further Reading

Qamar, M. A., Rota, S., Batzu, L., Subramanian, I., Falup-Pecurariu, C., Titova, N., Metta, V., Murasan, L., Odin, P., Padmakumar, C., Kukkle, P. L., Borgohain, R., Kandadai, R. M., Goyal, V., & Chaudhuri, K. R. (2023). Chaudhuri’s Dashboard of Vitals in Parkinson’s syndrome: an unmet need underpinned by real life clinical tests. Frontiers in neurology, 14, 1174698. https://doi.org/10.3389/fneur.2023.1174698