Short Report on DRIG’s Spring Conference 2018

By Marc van Grieken, DRIG Chairman

 

On Tuesday 26th June, the recently established Dundee Research Interest Group (DRIG) held its first public event: a conference with the title ‘Unveiling some of the Mechanisms which trigger Parkinson’s’.

The event was attended by approximately 80 people either directly, by having Parkinson’s or indirectly (as family member or carer) affected by Parkinson’s and addressed by 5 speakers and 5 PhD Students and postdoctorial researchers.

Prof Ken Bowler introduced the history and successes of the Edinburgh Research Interest Group which was the first one to be set up in the UK and his talk was followed by Marc van Grieken who gave a brief personal account of his diagnosis and the years following this.

The main part of the event however comprised three in depth presentations:

Firstly by Prof Dario Alessi who explained the discovery of specific pathways and mutated genes (LRRK2) that trigger Parkinson’s and by identifying these pathways open up the opportunity to ‘block’ or inhibit the effect of these.

He was followed by Dr Esther Sammler who is both a clinical neurologist consultant but also researches at Dario Alessi’s MRC unit concentrating on inhibiting the mutated gene and who is about to commence on sampling a test the researchers have developed

The final talk was by Dr Mitatul Muqit who studies two further genes PINK1 and Parkin and is setting out a framework for clinicians to increase and translate knowledge and understanding leading to better treatments.

The talks were followed by Q&A sessions and there was also time to talk on an individual basis to the researchers and students.

First DRIG event

The first DRIG event took place on June 26th 2018.

About 80 participants were offered a programme ranging from basic research to trial application to the patient. The scientific program was rounded off by a lecture from a very personal perspective by Parkinson patients, a time-lapse journey through the history of the Research Interest Groups and by young scientists who presented their work with great commitment and discussed it with the participants.

A big thank you to everyone contributing to this event and making it a successful start for DRIG.

Some impressions of the event.

Interaction Sessions

This session is intended to start the communication between the Parkinson’s professionals and patients. Patients should get to know what they can expect and professionals should get to know the needs of the patients first hand.

Available researchers, scientists, professionals and Parkinson’s UK representatives:

Professionals, Researchers, DRIG Officials

Occupation

Description – Statement

Speakers

Prof. Dario Alessi Professor of Signal Transduction and Director of MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) and the Division of Signal Transduction Therapy Unit (DSTT) I believe that it is not unrealistic that with continued and expanded research efforts, major strides towards better treating Parkinson’s disease can be made in the coming years. Patient’s support and involvement in research is vital for success!
Dr. Esther Sammler Postdoctoral Researcher and Honorary Senior Clinical Lecturer My specialist clinical interests are movement disorders, in particular Parkinson’s disease and related Parkinsonian syndromes as well as neurogenetics. I chair the Tayside Parkinson’s forum.
Dr. Miratul Muqit Wellcome Trust Senior Research Fellowship in Clinical Science and Programme Leader My laboratory focuses on elucidating signal transduction pathways that are linked to neurodegeneration in Parkinson’s disease … This will undoubtedly drive new ideas into how to better diagnose and treat this devastating condition.

Researchers

Dr. Sophie Burel Postdoctoral researcher with Dario Alessi, Miratul Muqit, MRC-PPU Using patients derived samples to study LRRK2 and PINK1, two proteins whose function is altered in Parkinson’s disease, which will hopefullly increase our knowledge about the mechanisms involved in the development of the disease, and might help to improve diagnosis and treatment.
Elena Purlyte PhD student with Dario Alessi, MRC-PPU I am looking for interactors of the Parkinson’s disease associated kinase LRRK2 – it is important work necessary to establish how LRRK2 acts in the cell and identify new potential drug targets.
Dr. Andy Howden Postdoctoral researcher with professor Doreen Cantrell, Cell Signalling and Immunology, SLS Dundee Understanding the link between the immune system and Parkinson’s disease.
Theresita Joseph 4th year medical student from University College London, MSc Research student with Dario Alessi Working on Masters to pursue clinical and research interests in Parkinson’s.
Dr. Valentina Ferlito Brainwave Discovery Ltd., Parkure Ltd., The University of Edinburgh CrowdLabbing: Learn how to participate in laboratory research to find new treatments for Parkinson’s and to become a citizen scientist.

Parkinson’s Specialist

Catherine Young Parkinson’s Nurse, Dundee Role of a Parkinson’s Nurse

Parkinson’s UK

John Minhinick Chairman Parkinson’s UK Fife Branch, Member of DRIG Steering Committee Offerings of the Fife Branch
Billy Webster Chairman Parkinson’s UK Dundee Branch, Member of DRIG Steering Committee Offerings of the Dundee Branch
Mary Elmers Parkinson’s UK, Service Improvement Adviser Parkinson’s Excellence Network and Parkinson’s Voices
Chloe Macmillan Parkinson’s UK, Area Development Manager Information & Support services available from Parkinson’s UK
Liz Nash Parkinson’s UK, Research Support Network Manager Research Support Network and Research participation opportunities

DRIG

Marc van Grieken Chairman DRIG Goals and future offerings from DRIG
Werner Remmele Secretary DRIG Goals and future offerings from DRIG

 

Prof Dario Alessi

Dario received his BSc in Biochemistry from the University of Birmingham in 1988 and obtained a Ph.D. in 1991 for his work on the synthesis and use of spin-labelled ATP analogues to study muscle contraction under the joint supervision of Ian Trayer (University of Birmingham) and David Trentham FRS (National Institute of Medical Research, Mill Hill, London).  He then carried out postdoctoral research with Philip Cohen in the MRC PPU from 1991 to 1997, where he became fascinated by protein kinases and how they control almost all aspects of cell biology.

In 1998 Dario became a Programme Leader in the MRC PPU, and assumed the Directorship of the Unit in April 2012.  Dario has received many awards and honours, including the Colworth Medal in 1999 (Biochemical Society), membership of EMBO (2005), the EMBO Gold Medal (2005), and fellowship of the Royal Society of Edinburgh (2002), the Royal Society of London (2008), and the Medical Academy of Science (2012).

More about Dario

Dr Miratul Muqit

Miratul graduated in Medicine with Honours from the University of Edinburgh in 1997. He was awarded a prestigious Kennedy Scholarship to study Neurobiology at Harvard University undertaking Huntington’s disease research in Mel Feany’s laboratory in 2001. He obtained his PhD in 2007 from the UCL Institute of Neurology where he made a major contribution to the discovery of PINK1 kinase mutations in Parkinson’s disease under the supervision of Nicholas Wood FMedSci and David Latchman. In parallel he received clinical training at leading London teaching hospitals including the Hammersmith Hospital and the National Hospital for Neurology and Neurosurgery at Queen Square. He specialized in Movement Disorders under Andrew Lees FMedSci and Kailash Bhatia.

Miratul joined the MRC PPU as a Wellcome Trust Intermediate Clinical Fellow (Sponsor: Dario Alessi FRS) in 2008 to investigate how PINK1 mutations lead to neurodegeneration in Parkinson’s. He has been a Wellcome Trust Senior Clinical Fellow since 2013. Miratul has received multiple awards including the Queen Square Prize in Neurology (2006) and the Linacre Prize Lecture from the Royal College of Physicians (2013). He became a member of the EMBO Young Investigator Programme in 2017.

More about Miratul

Dr Esther Sammler

I am a clinician scientist with an interest in neurodegenerative conditions and how to accelerate the application of scientific basic research discoveries towards identifying biomarkers and hopefully treatments. After graduating from medical school and working in Germany, I entered the Scottish neurology training programme in 2009. In 2014, I obtained my PhD as a Wellcome Trust fellow supervised by Professor Dario Alessi FRS FRSE on the “Signalling pathway of the E3 ubiquitin ligase subunit FBXO7 and its role in hereditary Parkinsonism”. I was appointed consultant neurologist in NHS Tayside in 2016. My interest is in neurogenetics and Parkinson’s disease. For my research I continue to work in the MRC Protein Phosphorylation Unit.

More about Esther

Cells, energy control and Parkinson’s: The role of PINK1 and Parkin

Dr. Miratul Muqit

Abstract

My research is directed at defining key pathways in cells that are linked to the development of Parkinson’s and harnessing this knowledge to generate new ideas to prevent and treat the condition. Major advances in genetics have provided clues as to the key molecules that control such pathways however there remain fundamental gaps in our understanding of how these genes function in cells. In my laboratory we have been focused on the PINK1 and Parkin genes that represent the commonest genetic cause of Parkinson’s in patients under the age of 45.

In my presentation I will discuss how the PINK1 and Parkin genes cooperate very closely in cells to protect us against damage to ‘mitochondria’ which are energy-producing centres of our cells. Our work has spanned very basic experiments in cells, but we have recently obtained very strong evidence in humans of the relevance of the PINK1-Parkin pathway to Parkinson’s.

Our work provides a framework for Clinicians to translate our knowledge and test our findings in patients both for the development of better diagnostics and therapies against Parkinson’s.

Bench to bedside Parkinson’s Research

Dr. Esther Sammler

Abstract

The greatest unmet need in Parkinson’s are treatments that slow the relentless progression of its symptoms. The discovery of genetic changes in different genes that cause Parkinson’s have prompted new therapeutic approaches. LRRK2 is the most frequently mutated gene in Parkinson’s and LRRK2 inhibitor drugs have recently entered early clinical trial stages. However, many questions remain including markers of disease progression, biochemical markers for LRRK2 activation status and biomarkers for drug target engagement. These biomarkers will be necessary to confirm patient subgroups with high LRRK2 activity that might receive greater benefits from these therapies and ensure that the drug has the desired effect on the pathway targeted.

My talk will focus on a test that we have developed to measure LRRK2 activity in human peripheral blood and I will show very exciting data demonstrating the usefulness of this test.

For people interested in participating in research, I will also briefly mention a translational research project of mine (involving donating a blood sample) that will soon launch in the East and South East of Scotland.

LRRK2 in Parkinson’s

Prof. Dario Alessi

Abstract

My laboratory is focused on deciphering the molecular causes of Parkinson’s. We believe that if we can comprehend what causes Parkinson’s, this will enable Researchers, Clinicians and Pharmaceutical Companies to work together to develop better ways to diagnose and treat the condition in the future. The approach we are taking is to study how mutations in certain genes cause Parkinson’s. One of the genes that we are working most on is called “LRRK2”. The LRRK2 gene is one of the most commonly mutated genes that causes familial inherited Parkinson’s. The LRRK2 gene encodes for a protein that is called the “LRRK2 enzyme”. Important research by our laboratory and others has shown that Parkinson’s mutations activate the LRRK2 enzyme.

This has led to the suggestions that drugs that target the LRRK2 enzyme could be developed for the better treatment of Parkinson’s. Excitingly, a company called Denali, based in San Francisco has recently launched the first clinical trials to test this idea. Several other companies are expected to initiate LRRK2 Parkinson’s trials soon.

These new drugs have the potential to slow down the progression of Parkinson’s.  

I will talk about the highlights of our recent research that have led to the discovery of how the LRRK2 enzyme works to control the activity of another set of enzymes called Rab.  I will describe recent work that has resulted in the discovery that mutation in several other genes that cause Parkinson’s, are also excitingly linked to the LRRK2 and Rab enzymes. Our work is revealing that LRRK2 is at the centre of a physiological network which is critical to understanding Parkinson’s. I will explain that with this increasing knowledge of the genetics and biology underlining Parkinson’s, I feel optimistic.

I believe that it is not unrealistic that with continued and expanded research efforts, major strides towards better treating Parkinson’s disease can be made in the coming years. Patient’s support and involvement in research is vital for success!

Unveiling some mechanisms that trigger Parkinson’s

The loss of the brain’s ability to produce dopamine is the cause of Parkinson’s disease.

50 years ago levodopa was developed, which supplies the brain with the missing dopamine, and it is still the gold standard for treating Parkinson’s. In order to fight not only the symptoms but also the disease itself, to slow down or stop its progression, the mechanisms that bring the production of dopamine to a standstill must be recognised.

Researchers at the University of Dundee have discovered some of these mechanisms and are thus feeding hope for a novel treatment of the causes of Parkinson’s disease.

The DRIG Spring Conference 2018 is dedicated to this topic.

The event is aimed at anyone with an interest in Parkinson’s disease – patients, carers, healthcare professionals or anyone interested in learning more about the disease. Participation in the conference is free, but registration is still required.

In addition to the conference contributions of renowned scientists and experts, there will be an interaction session during which participants can exchange directly with scientists and professionals and thus stimulate further research.

Date: June 26, 15:30 – 19:00
Location: Invercarse Hotel, 371 Perth Road, Dundee, DD2 1PG

Programme

Time Topic Speaker
15:30 Registration and refreshments, Interaction Session
16:00 Opening by Marc van Grieten (MvG) and
Introduction of John Minhinick (JM) as chair of the conference
MvG
16:05 Introduction of Prof Ken Bowler
From Edinburgh to Dundee: Research Interest Groups – a success story
JM
Prof Ken Bowler
16:20 Introduction of MvG by JM
Perspective of a Person with Parkinson’s
JM
MvG
16:30 Introduction of Prof Dario Alessi
LRRK2 in Parkinson’s
Facilitated Q&A / discussion
JM
Prof Dario Alessi
17:10 Introduction of Dr. Esther Sammler
Bench to bedside Parkinson’s research
Facilitated Q&A / discussion
JM
Dr. Esther Sammler
17:30 Break and Interaction Session
18:10 Introduction of Dr. Miratul Muqit
Cells, energy control and Parkinson’s: the role of PINK1 and Parkin
Facilitated Q&A / discussion
JM
Dr. Miratul Muqit
18:30 Panel discussion and further Q&A
Panel: Ken Bowler, Dario Alessi, Esther Sammler and Miratul Muqit
JM
18:55 Conclusion and closing remarks MvG
19:00 End of Event

Please register for the event