The WPC Research Spotlight series in 2021 will do a deep dive with six outstanding scientists and their team members from six different countries.
The series will start with a deep dive to discuss neuromelanin, or the “black stuff” in the brain, followed by a timely discussion on COVID and PD and then a discussion on a-synuclein and how the disease develops over time will open the door to testing new therapeutic approaches. The latter part of the year will introduce us to a team working on the immune system and how they are trying to understand what suppressing the immune system means for Parkinson’s, followed by a discussion about where Parkinson’s starts, the brain or gut, and why not in both locations with different symptomatology emerging depending on the starting location? The series wraps up with a deep dive on mitochondria, a topic that was (is?) often overlooked and assumed to be fully explored, which we learn in this talk this is not the case.
Each interview is exciting and breathes great life into areas of research that need more exploration and more funding. Watch the talks and be sure to share with others. We rely on the research community to find new therapies and unlock the mysteries of PD. Be sure to thank a scientist and let them know you are grateful for their work and for choosing to be on Team Parkinson’s.
Research Spotlight 2021 series made possible with support from Supernus Pharmaceuticals.
Interviewer: Roger Barker, BA, MBBS, PhD, MRCP, FMedSci
WPC Vice President and Board member Professor of Clinical
Neuroscience and Honorary Consultant in Neurology at the University of Cambridge and at Addenbrooke's Hospital in Cambridge UK. He trained at Oxford and London and has been in his current position for over 20 years having completed an MRC Clinician Scientist Fellowship just prior to this. Read his full bio.
AGENDA
Spotlight #1: Took place on January 26, 2021 with Professor Miquel Vila and colleagues. Spotlight #2: Took place on March 23, 2021 with Professor David Finkelstein and colleagues. Spotlight #3:
Took place on May 6, 2021 with Professor Erwan Bezard and colleagues. Spotlight #4:
Took place on June 22, 2021
with Professor Caroline Williams-Gray and colleagues. Spotlight #5: Took place on September 1, 2021 with Professor Per Borghammer. Spotlight #6: Took place on November 15, 2021 with Professor Heidi McBride
Research Spotlight on Professor Miquel Vila was joined by his colleague and post-doc, Ariadna Laguna and together they discussed the research his team is doing that is looking at neuromelanin in the brain. Despite the long-known connection between loss of pigmentation in the brain and Parkinson's, there is still very little known about neuromelanin in the brain, and surprisingly very little pre-clinical research has been done to understand the connection. Professor Vila writes in his blog on this topic about how animals used in research lack this black pigmentation, so unlike humans loss of this "black stuff" cannot be tracked or measured in animals. It's wholly unique to humans and this is a fascinating area to study.
Researcher: Miquel Vila, MD, PhD obtained his MD degree from the University of Barcelona and a PhD in Neuroscience from the University of Paris. He received his PhD training at the Salpêtrière Hospital in Paris under the supervision of Dr. Etienne C. Hirsch, devoted to the study of the functional consequences of dopaminergic neurodegeneration on the functioning of the basal ganglia. He then worked as a postdoctoral researcher at the laboratory of Dr. Serge Przedborski at Columbia University in New York, where he subsequently obtained a position as an Assistant Professor of Neurology, focusing on the molecular mechanisms of neuronal death in Parkinson's disease. Currently, he is a Professor at the Catalan Institution for Research and Advanced Studies (ICREA) and leads the Neurodegenerative Diseases Research Group at the Vall d’Hebron Research Institute in Barcelona.
Researcher: Ariadna Laguna, PhD is a senior researcher and principal investigator at the Neurodegenerative Diseases Research Group of the Vall d’Hebron Research Institute (VHIR) since December 2016, first funded by a Young Investigator contract from the Spanish Ministry of Economy and Competitiveness (MINECO), and currently by a Junior Leader contract from La Caixa
Banking Foundation. Dr. Laguna’s scientific career has been focused in understanding the molecular and cellular mechanisms underlying human diseases affecting the central nervous system, either with a neurodevelopmental or
a neurodegenerative etiology. First, with a PhD at the Center for Genomic Regulation (CRG, Barcelona, Spain) focusing on Down Syndrome. Next, with a postdoctoral period at the Karolinska Institutet (KI, Stockholm, Sweden) working
in transcription factors and Parkinson’s disease. Currently, focused on her own lines of research within the group of Neurodegenerative Diseases-VHIR (Barcelona, Spain) in the study of the metabolome and the microbiome in Parkinson’s
disease, with the aims of deciphering some key pathophysiological mechanisms, developing biomarkers and testing new modulatory therapeutic strategies. She has a broad experience in the field and a long experience in working
effectively as part of complex, international collaborations producing high-impact and high-value scientific results. Finally, she is active in training/mentoring (PhD, master and high school students) and outreach activities
to promote science and Parkinson’s disease awareness.
Research Spotlight on Professor David Finkelstein, Dr. Leah C. Beauchamp, Professor Kevin J. Barnham who discussed their recent research on COVID-19 and implications for Parkinson's. In their work, they demonstrated olfactory impairment in 75% of patients infected by the SARS-CoV=2 virus. Loss of sense of smell is an indicator of nervous system involvement and a 'red flag' for neuroscientists who see anosmia (inability to smell) as one of the first non-motor symptoms of pre-clinical Parkinson's disease. While there is no evidence that viruses cause Parkinson's there is a hypothesis that a virus could cause inflammation in the brain, which could prime it and make it more susceptable to neurodegeneration. The findings of their work is preliminary and needs further investigation. Until further is known, their work is a clarion call for vigilance in the neurology community to watch this virus closely and for governments to invest more funding to resesarch for neurodegenerative diseases like Parkinson's in order to prepare for a possible increase in cases in the coming years.
Researcher: Prof David Finkelstein trained as a neurophysiologist, giving him a broad systems wide approach to health and disease. David has embraced this systems physiology approach with the aim of translating work from the laboratory of bringing new compounds to the clinic. To this end, David has a holistic approach; recognising that to teamed up with People living with Parkinsons (PLWP), Clinicians and the biotechnology industry is needed to bring drugs to the clinic and improve the quality of life of PLWP. Over the last 5 year two compounds developed in his and Barnham labs, PBT434 (Alterity Biotechnology) and Cu(ATSM) (Collaborative Medicinal Development), have safely been tested in people (phase 1 trials) and are planned for further testing in People Living with Parkinsons and Multiple systems atrophy. Currently on the Board of a Parkinson’s Victoria and chair Parkinson’s Victoria research committee. David is on editorial boards for scientific journals and has published over 200 articles on the biology of PD.
Researcher: Dr. Leah Beauchamp recently completed her Ph.D. studies in the Barnham Neurotherapeutics Lab. Her area of interest is understanding prodromal Parkinson’s disease with the hope to develop new and accurate diagnostic tools. Leah has an expertise in olfaction (smell) and olfactory deficits that present in early Parkinson’s disease. Her work has helped to identify potential causes of this common symptom and this mechanism is being investigated in patients, with the hope of developing a novel diagnostic aid. More recently, Leah has focused her efforts on understanding the nature of neurological consequences of COVID-19. She is currently running trials to understand the nature of olfactory deficits in people suffering ‘long COVID syndrome’, as well as animal studies to help uncover the mechanism of this dysfunction.
Researcher: Prof Kevin J. Barnham is a graduate of The University of Queensland with a PhD in Chemistry and an interest in the development of new therapeutic compounds. Following his PhD he undertook work on new platinum based anti-cancer drugs at The University of London. Upon returning to Australia he joined The University of Melbourne in order to develop new therapies for Alzheimer’s disease. In 2011 he joined the Mental Health Research Institute which subsequently merged with The Florey Institute. Barnham has published over 200 scientific papers and is a consultant to local Biotech companies. The primary goal of the Barnham Laboratory (Neurotherapeutics) is to develop new drugs for neurodegenerative diseases such as Alzheimer's and Parkinson's. A number of these new drugs have demonstrated positive outcomes in multiple animal models of these diseases and more importantly have shown promise in subsequent human clinical trials.
Research Spotlight on Professor Bezard will be joined by his colleagues, Dr. Benjamin Dehay and Dr. Marie-Laure Arotcarena to discuss their recent research, based on earlier research on a-synuclein, showing that pathological forms of the a-synuclein protein present in the brain of deceased PD patients were capable of initiating a Parkinsonian-like pathological process in mice and primates. Their more recent recent research shows that extracted α-synuclein aggregates of brains during autopsy have the ability to initiate and extend the neurodegenerative process that typifies PD in mice and primates. Using the same human aggregates, this study shows that, not only does α-synuclein spread from the gut to the brain, but it also travels from the brain to the gut. Understanding how the disease develops over time should open the door to the development and testing of new therapeutic approaches.
Researcher: Dr. Erwan Bezard, PhD Research Director, has authored or co-authored over 300 professional publications in the field of neurobiology, most of which are on Parkinson's disease and related disorders. Bezard has funded in 2010, and headed until 2020, a CNRS research unit located in Bordeaux, the Institute of Neurodegenerative Diseases, which features preclinical and clinical researchers working towards development of therapeutic solutions. He is also a Visiting Professor at the China Academy of Medical Sciences (Beijing, China) where he has set-up and manages a non-human primate facility dedicated to Movement Disorders. He serves on the board of international organizations such as the Michael J. Fox Foundation and Parkinson’s UK. He is Associate Editor of Neurobiology of Disease, a leading journal in the field and serves on the editorial boards of several other neurobiology journals.
Researcher: Dr. Marie-Laure Arotcarena is a research engineer in the team of Erwan Bezard at the Institute of Neurogenerative Diseases in Bordeaux. After an engineering school degree, she had the opportunity to join the team of Erwan Bezard in 2016 to pursue with a PhD. Her PhD work aimed to establish a multifactorial and translational approach through modeling, mechanistic and therapeutic aspects associated with synucleinopathies. She focused on dissecting the underlying α-synuclein-mediated mechanisms of neurodegeneration in a non-human primate model of Parkinson’s disease and on assessing potential therapeutic strategies to restore the autophagy-lysosomal pathway in different models of synucleinopathy. She obtained her PhD in 2019 and pursue with one year of post-doctoral research supported by a France Parkinson grant with the objective of evaluating a chaperone-mediated autophagy-based therapeutic strategy in a non-human primate model of Parkinson’s disease. She is currently enrolled in multiple research projects developed in Erwan Bezard’s team as a research engineer and contributes to understand the role of α-synuclein protein into the Parkinson’s disease pathology and to discover new potential therapeutic targets for synucleinopathies.
Researcher: Benjamin Dehay, PhD obtained his PhD from the University of Paris VI in 2007, under the supervision of Dr. Anne Bertolotti, in the context of Huntington’s disease. He was then trained as a postdoctoral researcher at the laboratory of Dr. Miquel Vila in Barcelona, where his work mainly focused on the molecular mechanisms of neuronal cell death and the mechanism and significance of Lewy body formation in Parkinson’s disease. Since 2010, he has been working in the Institute of Neurodegenerative Diseases Research Group of Dr. Erwan Bezard, first as a senior postdoctoral fellow, where he subsequently obtained an Independent Investigator position as an INSERM Research Associate in 2013. Dr. Dehay’s scientific career has been focused to understand how the disease proteins cause alterations of the autophagy-lysosomal pathway, contributing to the pathogenesis for then proposing adapted therapeutic approaches to clear the toxic proteins and halt the disease process. He has a broad expertise in the field and in molecular and cell biology approaches and pathophysiological investigations in animal models including non-human primates, rodent models and on human tissues. Finally, some of the scientific highlights include the study of the progressive spreading of synucleinopathy through disease modeling across species.
Research Spotlight on on Professor Caroline Williams-Gray and her colleagues, Dr. Julia Greenland, and Dr. Antonina Kouli.
Learn more about this research by downloading and reading this recent article.
Researcher: Caroline Williams-Gray, MRCP, PhD is an MRC Clinician Scientist and Honorary Consultant Neurologist based in the UK. She completed undergraduate medical training at the University of Cambridge and then Oxford Clinical School in 2001, and obtained her PhD from Cambridge in 2008. She is now a Principal Investigator in the Department of Clinical Neurosciences at Cambridge University. The overarching aim of her research is to better understand the clinical heterogeneity of Parkinson’s disease and the underlying biological basis of this, with the ultimate goal of developing more targeted therapies for different Parkinson’s subtypes. Using epidemiological, functional neuroimaging and genetic approaches, her work to date has defined and characterised distinct cognitive syndromes in PD, and developed predictive tools for dementia risk and poor outcome which can be used on an individual patient basis. Her research group now primarily focuses on the role of the immune system in mediating clinical variability in PD and PD dementia; through studying blood and CSF-based markers, PET neuroimaging and neuropathology in stratified PD cohorts. She is also leading a clinical trial of the immunosuppressive drug, azathioprine, for Parkinson’s disease.
Researcher:
Julia Greenland, PhD is a neurology registrar in Addenbrookes Hospital, Cambridge and has been working as a clinical research associate in the Williams-Gray group since 2018. She completed her undergraduate medical training at Newcastle University in
2011, which included an intercalated MRes looking at the interplay between gait and cognition in Parkinson’s disease. She then worked as a medical junior on rotations through the North-East and East of England deaneries. Her current role involves setting up and running a clinical trial of azathioprine, an immunosuppressant medication, in early Parkinson’s disease, as a potential disease-modifying agent.
Researcher:
Antonina Kouli, PhD is a Postdoctoral Research Associate working with Dr Caroline Williams-Gray and a Junior Research Fellow at Wolfson College, Cambridge. Antonina completed her undergraduate studies in Biology at the University of Patras in Greece in
2013. She then moved to the UK where she obtained her MSc Neuroscience from University College London. In 2015, Antonina joined the laboratory of Prof Roger Barker and Dr Caroline Williams-Gray to undertake her PhD entitled "The
neuroinflammatory basis of disease progression and cognitive impairment in Parkinson’s disease". Her current research aims at better understanding the role of the immune system in Parkinson’s disease and its associated dementia.
This work involves neuropathological investigation of human postmortem tissue, analysis of immune-related biomarkers in the blood and cerebrospinal fluid, as well as PET neuroimaging in Parkinson's patients and healthy controls.
Articles:
Greenland JC, Cutting E, Kadyan S, Bond S, Chhabra A, Williams-Gray CH.
Azathioprine immunosuppression and disease modification in Parkinson's
disease (AZA-PD): a randomised double-blind placebo-controlled phase II
trial protocol. BMJ open. 2020;10(11):e040527. https://bmjopen.bmj.com/content/bmjopen/10/11/e040527.full.pdf
Wijeyekoon
RS, Kronenberg-Versteeg D, Scott KM, Hayat S, Kuan WL, Evans JR, Breen
DP, Cummins G, Jones JL, Clatworthy MR, Andres Floto R, Barker RA,
Williams-Gray CH. Peripheral innate immune and bacterial signals relate
to clinical heterogeneity in Parkinson's disease. Brain, behavior, and
immunity. 2020;87:473-88. https://doi.org/10.1016/j.bbi.2020.01.018
Wijeyekoon
RS, Moore SF, Farrell K, Breen DP, Barker RA, Williams-Gray CH.
Cerebrospinal Fluid Cytokines and Neurodegeneration-Associated Proteins
in Parkinson's Disease. Movement disorders : official journal of the
Movement Disorder Society. 2020;35(6):1062-6. https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.28015
This Research Spotlight features Professor Per Borghammer. Parkinson's disease (PD) probably consists of multiple subtypes, which explains why PD varies so much from person to person. There has been a lot of research into where in the body PD begins with a lot of focus on the gut and the brain.
Dr. Borghammer hypothesizes that there is a subtype of PD that starts in the gut and a different subtype that begins in the brain.
Researcher: Per Borghammer, MD, PhD is a professor of Nuclear Medicine & Neuroscience, Medical Faculty of Aarhus University. He specializes in clinical imaging of neurodegenerative disorders, in particular Parkinson’s disease. Dr. Borghammer’s research involves understanding the early and prodromal phase of Parkinson’s disease (PD). His research focuses mainly on the etiopathogenesis of PD, in particular the prion-like spreading of alpha-synuclein and whether PD in some cases originates in the peripheral autonomic nervous system. Dr. Borghammer employs a highly multi-disciplinary approach, including in depth characterization of patient cohorts using multi-modality imaging, histological studies of archived patient tissues, epidemiological studies, and mechanistic studies in experimental animal models of PD. In addition, his group is developing a range of PET tracers and other objective imaging markers to study non-motor dysfunction in PD. Most notably, he pioneered the development of novel PET imaging techniques to quantify the loss of parasympathetic innervation to internal organs.
This Research Spotlight features Dr. McBride discussing the challenges of studying Parkinson's across scales (molecules to cell biology to tissues and interconnectiveness of disease progression). The talk included some personal aspects of her family experience with PD, plus the roadblocks that are in place due to the culture of science (the lone genius who wins the big prize).
Researcher: Dr. McBride is a full Professor at McGill University in the Department of Neurology and Neurosurgery located within the Montreal Neurological Institute. As a basic science lab focused on mitochondrial biology, they aim to apply and test mechanistic discoveries within multiple disease paradigms, including Parkinson's disease. Working within a multidisciplinary team of investigators that include neuroscientists, immunologists and microbiologists, they explore how infection may promote disease, and the mechanistic contributions of disease-linked proteins including PINK1, Parkin, LRRK2 and Vps35.6
