WELCOME TO SYMPATH

Reach α-Synuclein mediated pathology

OUR AIM

SYMPATH aims to advance curative therapy for α-Synucleinopathies:

Goal 1

 

 

Clinical trials for novel immune therapy

Goal 2

 

 

Development of a diagnostic assay

Goal 3

 

 

Engage patients and researchers

Goal 1

 

 

Clinical trials for novel immune therapy

Goal 2

 

 

Development of a diagnostic assay

Goal 3

 

 

Engage patients and researchers

ABOUT THE PROJECT

 

SYMPATH was an EU-funded research project within FP7 with the vision of advancing a disease modifying therapy for Parkinson’s disease (PD) and multiple system atrophy (MSA). These neurodegenerative disorders belong to a group of diseases referred to as α-Synucleinopathies. They are characterised by aggregates of the protein α-Synuclein (α-Syn) in the brain referred to as Lewy bodies. A causal therapy is currently not available and available treatments merely alleviate the symptoms. Therefore, patients suffering from α-Synucleinopathies face an inevitable disease progression. The SYMPATH project was managed and brought to a successful conclusion by AFFiRiS AG in close cooperation with biolution GmbH.

PROJECT INFORMATION

Call: HEALTH-F4-2013-60299
Scientific officer: Jürgen Sautter
Coordinator: Mag. Vera Bürger
EU funding: EURO 5.89 million (total budget EURO 7.69 million)
Duration: 48 months from 1 April 2013 to 30 September 2017

Contact: office@sympath-project.eu

FUNDING INFORMATION

The EU project ‘SYMPATH’ was a collaborative project of the Seventh Framework Programme of the European Union with the Grant Agreement No.: FP7-HEALTH-2013-1.3-3: 602999

CORDIS LINK

WE COLLABORATE IN EUROPE

Eight excellent partners in three countries advised by outstanding experts

Mag. Vera Bürger
AFFiRiS AG 

Dr Iris Grünert
biolution GmbH

Prof. Wassilios Meissner
University Hospital Bordeaux 


Claire Levy Marchal, MD,MSc
INSERM F-CRIN Toulouse 

 

Prof. Dr Werner Poewe
Medical University of Innsbruck

Prof. Dr Dieter Willbold
Forschungszentrum Jülich GmbH

Prof. Olivier Rascol
University Hospital
Toulouse

We Target Parkinson’s Disease and MSA

Synucleinopathies: There is currently no cure for α-Synuclein mediated pathologies

Neurodegenerative diseases characterised by aggregates of the protein α-Synuclein (α-Syn) are referred to by the umbrella term α-Synucleinopathies. They are chronic, progressive disorders without curative therapy and include Parkinson’s disease and multiple system atrophy amongst other diseases.

α-Syn is widely expressed in the brain. There is increasing evidence that misfolded aggregated α-Syn is the causative agent in synucleinopathies, which has constituted a significant advance in our understanding of these diseases. This realisation provides a strong rationale to target α-Syn for developing a causative therapy and as a predictive biomarker for disease progression.

Parkinson’s disease

is the second most common neurodegenerative disorder, with approximately 1.2 million European patients alone.

FACTS:

  • Globally 10 M patients with 1.2 M in Europe
  • Life changing, but not life threatening
  • No cure, but symptomatic therapy

Parkinson’s disease is characterised by typical key motor symptoms (bradykinesia, rigor, tremor and postural instability) resulting in slowness and stiffness of movements, imbalance and ‘shaking’ of extremities and / or other parts of the body. In addition, non-motor symptoms have been well established such as loss of the sense of smell and disturbed sleep regulation (neuropsychiatric-, gastrointestinal-, autonomous symptoms). Interestingly, some of the non-motor symptoms start well before the classical motor symptoms are established.

Degeneration of dopaminergic neurons in specific parts of the brain (e.g. substantia nigra) are the pathological correlate of the motor symptoms in Parkinson’s disease. Currently, therapeutic measures are mostly aimed at raising dopamine in the brain and are thus restricted to offering symptomatic relief without perspective to alter or halt disease progression.

Multiple system atrophy

MSA is a rare, orphan status
neurodegenerative disorder.

FACTS:

  • Rare disease with prevalence 1/20,000
  • Fatal within 10 years after disease onset and no approved therapy
  • Aggressive disease progression

MSA progresses rapidly leading to death of the affected individual within 10 years (on average) after disease onset (on average). Its pathological hallmark is α-Syn aggregates within the cytoplasm of oligodendroglial cells, which provide support and protection to the nerve cells. As the disease progresses, the affected cells die off eventually leading to the onset of symptoms.

Unlike Parkinson’s disease, where symptomatic treatments are well established, there are no drugs approved for the treatment of multiple system atrophy.

WE FOLLOWED AN INNOVATIVE STRATEGY

Immunotherapies have an enormous clinical potential which needs to be raised by innovative approaches

Immune therapies tackling chronic diseases have become a major focus of biomedical research. Directing the immune system towards neurodegenerative diseases constitutes an innovative path towards reducing or even stopping disease progression. Although immune therapies against neurodegenerative disorders have been subject of intensive research, no concept has as yet entered clinical practice. The aim of SYMPATH is to advance clinical testing of therapeutic vaccine candidates targeting Parkinson’s disease and multiple system atrophy.

FACTS:

  • 66 patients recruited for clinical trials
  • 2 compounds evaluated for safety and tolerability
  • 1 diagnostic assay to measure α-Syn aggregates assessed

Coordinator AFFiRiS identified within a preclinical screening programme a series of α-Syn vaccine candidates. Two, PD01A and PD03A, were selected for early clinical development based on a set of features including the specificity of the immune response they induce, and promising results of proof of concept studies in various animal models and their favourable safety profile obtained by standard toxicity testing.  PD01A and PD03A represent, developmentally, the most advanced members of the α-Syn-targeting vaccine family.

Therefore, SYMPATH implemented a clinical strategy to test these two therapeutic vaccine candidates in Parkinson’s disease and multiple system atrophy. Patients were recruited at the earliest possible time point after confirmed diagnosis, vaccinated and followed for several months.

WE GENERATE SUBSTANTIAL IMPACT

Advancing immunotherapies targeting neurodegenerative diseases to improve clinical management of Parkinson’s disease and MSA

MAIN APPROACH

 

Immunotherapeutic approaches could deliver a novel, and cost/risk/benefit effective treatment modality exerting, in addition to standard of care, symptomatic and potentially disease modification in Parkinson’s disease and multiple system atrophy. This would constitute not only a scientific breakthrough, but would also fundamentally change the management and burden of synucleinopathies.

The SYMPATH consortium implemented a research programme to evaluate the safety and explore the activity of immunotherapy candidates targeting Parkinson’s disease and MSA in humans. The cause of both synucleinopathies are not fully understood and currently there are no treatment options available to alter the course of the diseases. A part of the programme is devoted to the identification of biomarkers with diagnostic and prognostic value, as for curative approaches of neurogenerative diseases it will not only be essential to identify patients as early as possible to initiate treatment before patients’ irreversible brain damage. Moreover, such assays are essential to assess the therapy response in treated patients to unequivocally evaluate disease progression as soon as possible.

Clinical trials establish safety and tolerability of the novel vaccine candidates

2 clinical trials were conducted to establish the safety and tolerability of PD01 and PD03 in patients suffering from Parkinson’s disease and MSA at clinical sites in Bordeaux, Innsbruck, Toulouse and Vienna.

Both compounds were found to be safe and tolerable and induced a clear dose dependent immune response not only against the vaccine but also the α-Syn epitope.

Both trials are registered at ClinicalTrials.gov, which is a Web-based resource that provides public access to information on clinical studies. The results of our two studies will be updated and can be accessed in the future through the following links:

NCT02270489: PD01A and PD03A in Patients with Early MSA (AFF009)
NCT02267434: PD03A in Patients with Early Parkinson’s Disease (AFF011)

Assays successfully adapted, paving the way towards biomarker development

The project successfully adapted the sFIDA technology (surface-based fluorescence intensity distribution analysis) for quantitative analysis of aggregated α-Syn in different body compartments such as plasma and CSF. It enables an assessment of the theragnostic value of α-Syn aggregates as a novel biomarker. Clinical samples were used to explore the correlation between stage of disease and detectable α-Syn aggregates.

SYMPATH events engage and enthuse researchers and a wider public

With the public event SYMPATH FAHR-MIT, public awareness of the project was raised and close interaction with patient organisations and clinicians was achieved. The tour brought the topic of Parkinson’s disease to a much wider public and should serve as a model for similar events.

OUTLOOK

PROSPECTS FOR VACCINE CANDIDATES IN PHASE II DESIGN

 

Based on the individual safety profile and immunogenic capacity one out of the two candidates tested will be selected for further development.

SPIN-OFF COMPANY FOR DIAGNOSTIC ASSAY FOUNDED

 

A biomarker for the diagnosis of neurodegenerative diseases would be invaluable, as cognitive performance tests are highly variable. Currently, there are no objective parameters to diagnose and assess synucleinopathies. The progress made through the development of a diagnostic assay will lead to the founding of a spin-off company in Q1 2018.

 

SYMPATH FAHR-MIT EVENT AS MODEL

 

The close interaction between patients, patient organisations and clinicians achieved through FAHR-MIT was exceptional and should serve as a model for similar events in the future.

 

SYMPATH FAHR-MIT

SYMPATH FAHR-MIT

© Helmut Kronewitter

Research projects face the difficult task of communicating complex scientific issues to the general public. It is a particular challenge to explain the potential medical progress of a clinical trial without raising exaggerated expectations, particularly in those affected and their families. SYMPATH successfully met this challenge through a bike tour aimed at putting different interest groups in contact with each other.

Promoting intense engagement with the subject and facilitating discussions, on an equal footing, between stakeholders was an integral part of our concept, which was developed together with patient organisations and participating clinicians. We took on board the wishes of Mag. W. Schmutz (Austrian National Association of Parkinson’s disease self-help groups – Lower Austria Chapter), who requested “not to talk about patients, but with them”.

The bike tour ran over seven consecutive days (Saturday 30th May 2015 to Friday 6th June 2015), with up to 16 Parkinson’s disease patients cycling a route (of up to 400km) which linked major centres between Innsbruck and Vienna in Austria. The tour even gave some of the participants the motivation and courage required to get back on their bikes. They were joined on this tour by experts, politicians and celebrities.

The tour concept was further realised through the welcome events which combined speeches from invited dignitaries and SYMPATH representatives with an informative travelling exhibition. The exhibition presented information about Parkinson’s disease and the SYMPATH project as well as incorporating interactive elements designed to simulate the symptoms of Parkinson’s disease.

© Helmut Kronewitter

The enthusiastic feedback from many participants provides strong evidence that we were able to do just that and even exceeded expectations. Thus, the bike tour has made an important contribution to the SYMPATH research project by establishing an open and critical discourse.

At the final event in Vienna, Marianne Klicka, the president of Vienna City Council, was present to support the event. She was so impressed that she spontaneously invited all project participants to a reception at Vienna City Hall in order to thank everyone involved for this outstanding event.

We are very pleased with the lively media interest, reflected in the many reports across all relevant media, which brought the topic of Parkinson’s disease to a much wider public.

Dr Iris Grünert who, along with her team at Biolution, organised the event, was pleased with the positive feedback, in particular on the part of the participating patients: “Cooperation with patient organisations has established valuable contacts, of which we will certainly benefit in the course of the project. I am glad that the patient organisations also considered this joint initiative a success”.

The event fulfilled (and exceeded) the requirements of many of the stakeholders involved, in particular the patients and patient organisations were impressed with the level of interaction the event afforded between themselves and the physicians. SYMPATH FAHR-MIT should serve as a model for similar events.

PROSPECTS FOR VACCINE CANDIDATES IN PHASE II DESIGN

 

Based on the individual safety profile and immunogenic capacity one out of the two candidates tested will be selected for further development.

SPIN-OFF COMPANY FOR DIAGNOSTIC ASSAY FOUNDED

 

A biomarker for the diagnosis of neurodegenerative diseases would be invaluable, as cognitive performance tests are highly variable. Currently, there are no objective parameters to diagnose and assess synucleinopathies. The progress made through the development of a diagnostic assay will lead to the founding of a spin-off company in Q1 2018.

 

SYMPATH FAHR-MIT EVENT AS MODEL

 

The close interaction between patients, patient organisations and clinicians achieved through FAHR-MIT was exceptional and should serve as a model for similar events in the future.

 

SYMPATH FAHR-MIT

SYMPATH FAHR-MIT

© Helmut Kronewitter

Research projects face the difficult task of communicating complex scientific issues to the general public. It is a particular challenge to explain the potential medical progress of a clinical trial without raising exaggerated expectations, particularly in those affected and their families. SYMPATH successfully met this challenge through a bike tour aimed at putting different interest groups in contact with each other.

Promoting intense engagement with the subject and facilitating discussions, on an equal footing, between stakeholders was an integral part of our concept, which was developed together with patient organisations and participating clinicians. We took on board the wishes of Mag. W. Schmutz (Austrian National Association of Parkinson’s disease self-help groups – Lower Austria Chapter), who requested “not to talk about patients, but with them”.

The bike tour ran over seven consecutive days (Saturday 30th May 2015 to Friday 6th June 2015), with up to 16 Parkinson’s disease patients cycling a route (of up to 400km) which linked major centres between Innsbruck and Vienna in Austria. The tour even gave some of the participants the motivation and courage required to get back on their bikes. They were joined on this tour by experts, politicians and celebrities.

The tour concept was further realised through the welcome events which combined speeches from invited dignitaries and SYMPATH representatives with an informative travelling exhibition. The exhibition presented information about Parkinson’s disease and the SYMPATH project as well as incorporating interactive elements designed to simulate the symptoms of Parkinson’s disease.

© Helmut Kronewitter

The enthusiastic feedback from many participants provides strong evidence that we were able to do just that and even exceeded expectations. Thus, the bike tour has made an important contribution to the SYMPATH research project by establishing an open and critical discourse.

At the final event in Vienna, Marianne Klicka, the president of Vienna City Council, was present to support the event. She was so impressed that she spontaneously invited all project participants to a reception at Vienna City Hall in order to thank everyone involved for this outstanding event.

We are very pleased with the lively media interest, reflected in the many reports across all relevant media, which brought the topic of Parkinson’s disease to a much wider public.

Dr Iris Grünert who, along with her team at Biolution, organised the event, was pleased with the positive feedback, in particular on the part of the participating patients: “Cooperation with patient organisations has established valuable contacts, of which we will certainly benefit in the course of the project. I am glad that the patient organisations also considered this joint initiative a success”.

The event fulfilled (and exceeded) the requirements of many of the stakeholders involved, in particular the patients and patient organisations were impressed with the level of interaction the event afforded between themselves and the physicians. SYMPATH FAHR-MIT should serve as a model for similar events.

WE SPREAD THE NEWS

Dedicated events in collaboration with patient organisations as well as researchers

PUBLICATIONS

Currently 6 research reports have been published within SYMPATH, and there are more to come!

View all publications

PUBLICATIONS

 


Multiple System Atrophy – State of the Art
May 2017
Laurens B, Vergnet S, Lopez MC, Foubert-Samier A, Tison F, Fernagut PO, Meissner WG
D.O.I. 10.1007/s11910-017-0751-0



Nanoparticle standards for immuno-based quantitation of α-synuclein oligomers in diagnostics of Parkinson’s disease and other synucleopathies

March 2015
Herrmann Y, Bujnicki T, Zafiu C, Kulawik A, Kühbach K, Peters L, Fabig J, Willbold J, Bannach O, Willbold D

D.O.I 10.1016/j.cca.2017.01.010



Active immunization therapies for Parkinson’s disease and multiple system atrophy.

August 2015
Achim Schneeberger MD, Lanay Tierney PhD, Markus Mandler PhD

D.O.I. 10.1002/mds.26377



Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations
June 2015
Benjamin Dehay, PhD†, Mathieu Bourdenx, MS†, Philippe Gorry, MD, Prof Serge Przedborski, MD, Miquel Vila, MD, Stéphane Hunot, PhD, Andrew Singleton, PhD, Prof C Warren Olanow, MD, Kalpana M Merchant, PhD, Prof Erwan Bezard, PhD’Correspondence information about the author Prof Erwan BezardEmail the author Prof Erwan Bezard, Prof Gregory A Petsko, PhD, Prof Wassilios G Meissner, MD

D.O.I. 10.1016/S1474-4422(15)00006-X



Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy

March 2015
Mandler M, Valera E, Rockenstein E, Mante M, Weninger H, Patrick C, Adame A, Schmidhuber S, Santic R, Schneeberger A, Schmidt W, Mattner F, Masliah E
D.O.I. 10.1186/s13024-015-0008-9



Targeting α-synuclein: Therapeutic options

Benjamin Dehay PhD, Mickael Decressac PhD, Mathieu Bourdenx PhD, Irene Guadagnino PhD, Pierre-Olivier Fernagut PhD, Anna Tamburrino PhD, Fares Bassil PhD, Wassilios G. Meissner PhD, Erwan Bezard P
March 2016
D.O.I. 10.1002/mds.26568

MEETINGS

Researchers from eight partner institutions met regularly forming a closely-knit network, which will support collaborations beyond the lifetime of the project. The total of six internal meetings were attended cumulatively by 133 participants indicating an intense scientific exchange.

View meeting impressions

EVENTS

Project dissemination partner biolution brought their expertise into play on 2 major events that took place as part of the SYMPATH project. SYMPATH FAHR-MIT targeted the general public and the SYMPATH SYMPOSIUM targeted the scientific community.

SYMPATH FAHR-MIT

SYMPATH FAHR-MIT

© Helmut Kronewitter

Research projects face the difficult task of communicating complex scientific issues to the general public. It is a particular challenge to explain the potential medical progress of a clinical trial without raising exaggerated expectations, particularly in those affected and their families. SYMPATH successfully met this challenge through a bike tour aimed at putting different interest groups in contact with each other.

Promoting intense engagement with the subject and facilitating discussions, on an equal footing, between stakeholders was an integral part of our concept, which was developed together with patient organisations and participating clinicians. We took on board the wishes of Mag. W. Schmutz (Austrian National Association of Parkinson’s disease self-help groups – Lower Austria Chapter), who requested “not to talk about patients, but with them”.

The bike tour ran over seven consecutive days (Saturday 30th May 2015 to Friday 6th June 2015), with up to 16 Parkinson’s disease patients cycling a route (of up to 400km) which linked major centres between Innsbruck and Vienna in Austria. The tour even gave some of the participants the motivation and courage required to get back on their bikes. They were joined on this tour by experts, politicians and celebrities.

The tour concept was further realised through the welcome events which combined speeches from invited dignitaries and SYMPATH representatives with an informative travelling exhibition. The exhibition presented information about Parkinson’s disease and the SYMPATH project as well as incorporating interactive elements designed to simulate the symptoms of Parkinson’s disease.

© Helmut Kronewitter

The enthusiastic feedback from many participants provides strong evidence that we were able to do just that and even exceeded expectations. Thus, the bike tour has made an important contribution to the SYMPATH research project by establishing an open and critical discourse.

At the final event in Vienna, Marianne Klicka, the president of Vienna City Council, was present to support the event. She was so impressed that she spontaneously invited all project participants to a reception at Vienna City Hall in order to thank everyone involved for this outstanding event.

We are very pleased with the lively media interest, reflected in the many reports across all relevant media, which brought the topic of Parkinson’s disease to a much wider public.

Dr Iris Grünert who, along with her team at Biolution, organised the event, was pleased with the positive feedback, in particular on the part of the participating patients: “Cooperation with patient organisations has established valuable contacts, of which we will certainly benefit in the course of the project. I am glad that the patient organisations also considered this joint initiative a success”.

The event fulfilled (and exceeded) the requirements of many of the stakeholders involved, in particular the patients and patient organisations were impressed with the level of interaction the event afforded between themselves and the physicians. SYMPATH FAHR-MIT should serve as a model for similar events.

SYMPATH SYMPOSIUM

SYMPATH Symposium on Targeting Synucleinopathies

 

© biolution GmbH

 

In order to achieve maximum visibility for the SYMPATH project within the scientific community a symposium was organised, in close cooperation between AFFiRiS and Biolution. Its aim was to bring together world-leading experts to discuss recent progress in developing new potential biomarkers and therapeutic concepts, including vaccines, for Parkinson’s disease (PD) and multiple system atrophy (MSA).

It was an important aim of the SYMPATH symposium organisers to complement the world-class research taking place within the SYMPATH project with a broad selection of world-leading external speakers. The SYMPATH Symposium on Targeting Synucleinopathies was a great success, bringing together an excellent selection of world-leading experts in SYMPATH related fields to present the significance of the project and its results in an appropriate context. Lively discussion was generated both in the symposium sessions and also in the plentiful informal discussion breaks and poster session.

The SYMPATH Symposium on Targeting Synucleinopathies itself attracted 115 attendees, many of whom were international, and also stimulated additional interest in many researchers of the Vienna Biocenter who interacted with the exhibition material. Highly positive feedback was received from many of the speakers and symposium attendees crediting the excellent range of speakers, the good organisation and the positive environment for discussion and scientific exchange.

PUBLICATIONS

Currently 6 research reports have been published within SYMPATH, and there are more to come!

View all publications

PUBLICATIONS

 


Multiple System Atrophy – State of the Art
May 2017
Laurens B, Vergnet S, Lopez MC, Foubert-Samier A, Tison F, Fernagut PO, Meissner WG
D.O.I. 10.1007/s11910-017-0751-0



Nanoparticle standards for immuno-based quantitation of α-synuclein oligomers in diagnostics of Parkinson’s disease and other synucleopathies

March 2015
Herrmann Y, Bujnicki T, Zafiu C, Kulawik A, Kühbach K, Peters L, Fabig J, Willbold J, Bannach O, Willbold D

D.O.I 10.1016/j.cca.2017.01.010



Active immunization therapies for Parkinson’s disease and multiple system atrophy.

August 2015
Achim Schneeberger MD, Lanay Tierney PhD, Markus Mandler PhD

D.O.I. 10.1002/mds.26377



Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations
June 2015
Benjamin Dehay, PhD†, Mathieu Bourdenx, MS†, Philippe Gorry, MD, Prof Serge Przedborski, MD, Miquel Vila, MD, Stéphane Hunot, PhD, Andrew Singleton, PhD, Prof C Warren Olanow, MD, Kalpana M Merchant, PhD, Prof Erwan Bezard, PhD’Correspondence information about the author Prof Erwan BezardEmail the author Prof Erwan Bezard, Prof Gregory A Petsko, PhD, Prof Wassilios G Meissner, MD

D.O.I. 10.1016/S1474-4422(15)00006-X



Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy

March 2015
Mandler M, Valera E, Rockenstein E, Mante M, Weninger H, Patrick C, Adame A, Schmidhuber S, Santic R, Schneeberger A, Schmidt W, Mattner F, Masliah E
D.O.I. 10.1186/s13024-015-0008-9



Targeting α-synuclein: Therapeutic options

Benjamin Dehay PhD, Mickael Decressac PhD, Mathieu Bourdenx PhD, Irene Guadagnino PhD, Pierre-Olivier Fernagut PhD, Anna Tamburrino PhD, Fares Bassil PhD, Wassilios G. Meissner PhD, Erwan Bezard P
March 2016
D.O.I. 10.1002/mds.26568

MEETINGS

Researchers from eight partner institutions met regularly forming a closely-knit network, which will support collaborations beyond the lifetime of the project. The total of six internal meetings were attended cumulatively by 133 participants indicating an intense scientific exchange.

View meeting impressions

EVENTS

Project dissemination partner biolution brought their expertise into play on 2 major events that took place as part of the SYMPATH project. SYMPATH FAHR-MIT targeted the general public and the SYMPATH SYMPOSIUM targeted the scientific community.

SYMPATH FAHR-MIT

SYMPATH FAHR-MIT

© Helmut Kronewitter

Research projects face the difficult task of communicating complex scientific issues to the general public. It is a particular challenge to explain the potential medical progress of a clinical trial without raising exaggerated expectations, particularly in those affected and their families. SYMPATH successfully met this challenge through a bike tour aimed at putting different interest groups in contact with each other.

Promoting intense engagement with the subject and facilitating discussions, on an equal footing, between stakeholders was an integral part of our concept, which was developed together with patient organisations and participating clinicians. We took on board the wishes of Mag. W. Schmutz (Austrian National Association of Parkinson’s disease self-help groups – Lower Austria Chapter), who requested “not to talk about patients, but with them”.

The bike tour ran over seven consecutive days (Saturday 30th May 2015 to Friday 6th June 2015), with up to 16 Parkinson’s disease patients cycling a route (of up to 400km) which linked major centres between Innsbruck and Vienna in Austria. The tour even gave some of the participants the motivation and courage required to get back on their bikes. They were joined on this tour by experts, politicians and celebrities.

The tour concept was further realised through the welcome events which combined speeches from invited dignitaries and SYMPATH representatives with an informative travelling exhibition. The exhibition presented information about Parkinson’s disease and the SYMPATH project as well as incorporating interactive elements designed to simulate the symptoms of Parkinson’s disease.

© Helmut Kronewitter

The enthusiastic feedback from many participants provides strong evidence that we were able to do just that and even exceeded expectations. Thus, the bike tour has made an important contribution to the SYMPATH research project by establishing an open and critical discourse.

At the final event in Vienna, Marianne Klicka, the president of Vienna City Council, was present to support the event. She was so impressed that she spontaneously invited all project participants to a reception at Vienna City Hall in order to thank everyone involved for this outstanding event.

We are very pleased with the lively media interest, reflected in the many reports across all relevant media, which brought the topic of Parkinson’s disease to a much wider public.

Dr Iris Grünert who, along with her team at Biolution, organised the event, was pleased with the positive feedback, in particular on the part of the participating patients: “Cooperation with patient organisations has established valuable contacts, of which we will certainly benefit in the course of the project. I am glad that the patient organisations also considered this joint initiative a success”.

The event fulfilled (and exceeded) the requirements of many of the stakeholders involved, in particular the patients and patient organisations were impressed with the level of interaction the event afforded between themselves and the physicians. SYMPATH FAHR-MIT should serve as a model for similar events.

SYMPATH SYMPOSIUM

SYMPATH Symposium on Targeting Synucleinopathies

 

© biolution GmbH

 

In order to achieve maximum visibility for the SYMPATH project within the scientific community a symposium was organised, in close cooperation between AFFiRiS and Biolution. Its aim was to bring together world-leading experts to discuss recent progress in developing new potential biomarkers and therapeutic concepts, including vaccines, for Parkinson’s disease (PD) and multiple system atrophy (MSA).

It was an important aim of the SYMPATH symposium organisers to complement the world-class research taking place within the SYMPATH project with a broad selection of world-leading external speakers. The SYMPATH Symposium on Targeting Synucleinopathies was a great success, bringing together an excellent selection of world-leading experts in SYMPATH related fields to present the significance of the project and its results in an appropriate context. Lively discussion was generated both in the symposium sessions and also in the plentiful informal discussion breaks and poster session.

The SYMPATH Symposium on Targeting Synucleinopathies itself attracted 115 attendees, many of whom were international, and also stimulated additional interest in many researchers of the Vienna Biocenter who interacted with the exhibition material. Highly positive feedback was received from many of the speakers and symposium attendees crediting the excellent range of speakers, the good organisation and the positive environment for discussion and scientific exchange.

WEBSITE

The content of the SYMPATH website was designed to deliver the projects aims and goals in a clear and targeted fashion, which addresses the various stakeholder groups identified for the SYMPATH project. This aim was achieved through the combination of a clear writing style, which avoids the unnecessary use of scientific jargon, and the provision of a comprehensive glossary of scientific terms.

Website

VIDEO

As part of the SYMPATH project a video was developed to inform people about the project and related themes.

The video concept was to address the following topics:
• Parkinson’s disease is a progressive neurodegenerative disorder without cure
• α-Synuclein is the molecular cause of the disease
• SYMPATH targets α-Synuclein to develop a disease modifying therapy

Watch the video

PHOTOBOOK

Biolution prepared this book from the many photographs, quotes and collected media reports generated during the tour. On 20th January 2016, the photobook was presented to SYMPATH FAHR-MIT participants at a special event held at the coordinator AFFiRiS.

 

View photobook impressions

WEBSITE

The content of the SYMPATH website was designed to deliver the projects aims and goals in a clear and targeted fashion, which addresses the various stakeholder groups identified for the SYMPATH project. This aim was achieved through the combination of a clear writing style, which avoids the unnecessary use of scientific jargon, and the provision of a comprehensive glossary of scientific terms.

Website

VIDEO

As part of the SYMPATH project a video was developed to inform people about the project and related themes.

The video concept was to address the following topics:
• Parkinson’s disease is a progressive neurodegenerative disorder without cure
• α-Synuclein is the molecular cause of the disease
• SYMPATH targets α-Synuclein to develop a disease modifying therapy

Watch the video

PHOTOBOOK

Biolution prepared this book from the many photographs, quotes and collected media reports generated during the tour. On 20th January 2016, the photobook was presented to SYMPATH FAHR-MIT participants at a special event held at the coordinator AFFiRiS.

 

View photobook impressions

IMPRESSIONS AND QUOTES

“The SYMPATH consortium, consisting of eight partners in three European countries, was initiated in 2013 with the goal to assess two AFFITOPE-based immunotherapies within two clinical studies in Morbus Parkinson and Multiple System Atrophy. It was amazing to see how the collaboration between all consortium partners developed at the occasion of SYMPATH project meetings, scientific meetings and by direct interaction. This complementary cooperation beyond borders combined with personal engagement enabled not only the timely completion of all tasks associated with SYMPATH but may support deeper insight into disease development and potential therapeutic approaches”.

Mag. Vera Bürger

AFFIRIS AG

“We have been privileged to have had the opportunity to work within the SYMPATH consortium for the past four years and are proud of all that we have accomplished together. The AFFITOPE-based immunotherapy in Parkinson’s disease performed within SYMPATH revealed that the immunogenicity profile looks encouraging and supports the hypothesis that patients elicit an antibody response specific to alpha-synuclein, a protein that is believed to be contributing to the pathogenesis of Parkinson’s disease. Clinical trials are a key research tool for advancing medical knowledge with the ultimate goals to improve patient care. Therefore, we would especially like to thank our highly motivated Austrian patients with Parkinson’s disease who participated in this immunotherapy trial and their families”.

Klaus Seppi, Atbin Djamshidian-Tehrani and Prof. Dr Werner Poewe,

Medical University of Innsbruck

After conducting the first-in-man Parkinson’s disease immunomodulation therapy as a single center in Vienna it was a great experience to work with an international team. The SYMPATH consortium gave us the opportunity to exchange thoughts and ideas around idiopathic Parkinson’s disease and multiple system atrophy therapies and opened new ways to communicate EU-wide with the other partners with whom we had fruitful discussions. Including support, group activities brought new insights into major unmet needs from the patients’ and caregivers’ perspective in numerous discussions. The attitude of laymen to participating in clinical trials has changed, as more people want to take part, whereas this was completely unimaginable beforehand”.

Dieter Volc, MD

Prosenex

“We are proud to be part of the SYMPATH consortium and feel that our expertise and skill in streamlining the administrative duties freed the scientists to focus on the research. It is great to know that we were thus able to contribute to the great scientific success of the project.”

“Presenting the SYMPATH project results in an appropriate context was of key importance to us and the symposium was a great success in facilitating this, bringing together an excellent selection of world-leading experts in SYMPATH related fields”.

Dr Iris Grünert

biolution GmbH

It was a pleasure and a privilege to be part of this amazing consortium. The SYMPATH partners’ expertise and the extent of their engagement was essential for the progress and success of the project. Certainly, this experience will be beneficial for us also in the future far beyond the project’s duration”.

Prof. Dr Dieter Willbold

Forschungszentrum Jülich

“SYMPATH is a complex, multi-partner and innovative project which illustrates the successful collaboration between institutional teams (MSA expert centers, Clinical Investigating Center of Toulouse, Institute of Neurodegenerative Diseases of Bordeaux, with the support of F-CRIN) and industry, in terms of recruitment achievement and tight agenda observance.”

Prof. Olivier Rascol

University Hospital Toulouse

“Working on the SYMPATH project was very enriching for INSERM, interfacing with industry and other institutional structures. This European project has been achieved successfully thanks to a smooth collaboration between every partner involved”.

INSERM team

INSERM FCRIN Toulouse

“We are extremely grateful and proud of having joined this great international consortium. For sure, we want to build on the success of this project and pave the way for our spin-off company ‘attyloid’ which will soon be founded”.

Dr Oliver Bannach

Forschungszentrum Jülich GmbH

“The SYMPATH consortium, consisting of eight partners in three European countries, was initiated in 2013 with the goal to assess two AFFITOPE-based immunotherapies within two clinical studies in Morbus Parkinson and Multiple System Atrophy. It was amazing to see how the collaboration between all consortium partners developed at the occasion of SYMPATH project meetings, scientific meetings and by direct interaction. This complementary cooperation beyond borders combined with personal engagement enabled not only the timely completion of all tasks associated with SYMPATH but may support deeper insight into disease development and potential therapeutic approaches”.

Mag. Vera Bürger

AFFIRIS AG

“We have been privileged to have had the opportunity to work within the SYMPATH consortium for the past four years and are proud of all that we have accomplished together. The AFFITOPE-based immunotherapy in Parkinson’s disease performed within SYMPATH revealed that the immunogenicity profile looks encouraging and supports the hypothesis that patients elicit an antibody response specific to alpha-synuclein, a protein that is believed to be contributing to the pathogenesis of Parkinson’s disease. Clinical trials are a key research tool for advancing medical knowledge with the ultimate goals to improve patient care. Therefore, we would especially like to thank our highly motivated Austrian patients with Parkinson’s disease who participated in this immunotherapy trial and their families”.

Klaus Seppi, Atbin Djamshidian-Tehrani and Prof. Dr Werner Poewe,

Medical University of Innsbruck

After conducting the first-in-man Parkinson’s disease immunomodulation therapy as a single center in Vienna it was a great experience to work with an international team. The SYMPATH consortium gave us the opportunity to exchange thoughts and ideas around idiopathic Parkinson’s disease and multiple system atrophy therapies and opened new ways to communicate EU-wide with the other partners with whom we had fruitful discussions. Including support, group activities brought new insights into major unmet needs from the patients’ and caregivers’ perspective in numerous discussions. The attitude of laymen to participating in clinical trials has changed, as more people want to take part, whereas this was completely unimaginable beforehand”.

Dieter Volc, MD

Prosenex

“We are proud to be part of the SYMPATH consortium and feel that our expertise and skill in streamlining the administrative duties freed the scientists to focus on the research. It is great to know that we were thus able to contribute to the great scientific success of the project.”

“Presenting the SYMPATH project results in an appropriate context was of key importance to us and the symposium was a great success in facilitating this, bringing together an excellent selection of world-leading experts in SYMPATH related fields”.

Dr Iris Grünert

biolution GmbH

It was a pleasure and a privilege to be part of this amazing consortium. The SYMPATH partners’ expertise and the extent of their engagement was essential for the progress and success of the project. Certainly, this experience will be beneficial for us also in the future far beyond the project’s duration”.

Prof. Dr Dieter Willbold

Forschungszentrum Jülich

“SYMPATH is a complex, multi-partner and innovative project which illustrates the successful collaboration between institutional teams (MSA expert centers, Clinical Investigating Center of Toulouse, Institute of Neurodegenerative Diseases of Bordeaux, with the support of F-CRIN) and industry, in terms of recruitment achievement and tight agenda observance.”

Prof. Olivier Rascol

University Hospital Toulouse

“Working on the SYMPATH project was very enriching for INSERM, interfacing with industry and other institutional structures. This European project has been achieved successfully thanks to a smooth collaboration between every partner involved”.

INSERM team

INSERM FCRIN Toulouse

“We are extremely grateful and proud of having joined this great international consortium. For sure, we want to build on the success of this project and pave the way for our spin-off company ‘attyloid’ which will soon be founded”.

Dr Oliver Bannach

Forschungszentrum Jülich GmbH

CONTACT

If you are interested in learning more about the SYMPATH project or collaborating scientifically with the SYMPATH project partners, the project coordinator welcomes your enquiries.

office@sympath-project.eu

 

SYMPATH PROJECT OFFICE

Dr Iris Grünert

biolution GmbH
Helmut-Qualtinger-Gasse 2/2
1030 Vienna, Austria

 

LEGAL NOTICE

The information on this site is subject to a disclaimer and a copyright notice.

LEGAL INFORMATION

LEGAL INFORMATION
Disclosure according to §5 ECG and §25 media law (Austria)
Please visit the WKO-Website

Publisher
AFFiRiS AG (Austria)

Basic direction
This web site provides information about the research project SYMPATH, which is funded by the European Union.  The mission of the website is to inform the general public and interested scientific community on background information of the project and progress of research as it becomes available. The information on the website is of a general nature and is not meant replace any advice or information provided by health care professionals.

HON Code certification
This site complies with the HONcode standard for trustworthy health information: verify here (https://www.healthonnet.org/HONcode/Conduct.html?HONConduct675866)

Important legal notice
The information on this site is subject to a disclaimer and a copyright notice.

 

COPYRIGHT NOTICE
All photographs copyright biolution GmbH unless otherwise stated. Photos must not be reproduced without permission of biolution GmbH or the copyright holder.

 

DISCLAIMER NOTICE
This web site contains information and files, individually and collectively the “information”, which is made available by SYMPATH and its publishers. All information is intended for internal use within the authorised website users. Our goal is to keep this information timely and accurate. If errors are brought to our attention, we will correct them as soon as possible. However, the publisher accepts no responsibility or liability whatsoever with regard to the material on this site. This material is: Information of a general nature only which is not intended to address the specific circumstances of any particular individual or entity. Not necessarily comprehensive, complete, accurate or up to date.

Please note that it cannot be guaranteed that a document available online exactly reproduces an officially adopted text, so that only European Union legislation published in the paper editions of the Official Journal of the European Communities is deemed authentic. It is our goal to minimise disruption due to technical errors. However, some data or information on our site may have been created or structured in files or formats that are not error-free and we cannot guarantee that our service will not be interrupted or otherwise affected by such problems. SYMPATH accepts no responsibility with regard to such problems, or the consequences thereof, incurred as a result of using this site. This disclaimer is not intended to contravene any requirements laid down in applicable national law nor to exclude liability for matters which may not be excluded under that law.

External links
This website provides links to websites which are considered helpful. These include national and international agencies and private organisations. We cannot confirm the accuracy of information provided by these websites. Links to a website does not constitute any endorsement by SYMPATH or its associates of the information or products presented on that website. Such websites are not within our control and may not follow the same privacy, security or accessibility policies. Once you visit such a website you are subject to the policies of that site. Links from the SYMPATH website to any other third-party website imply no endorsement by us of the website, company or product.

Use of google analytics / data privacy
This website uses Google Analytics, a web analytics service provided by Google, Inc. (“Google”). Google Analytics uses “cookies”, which are text files placed on your computer, to help the website analyse how users use the site. The information generated by the cookie about your use of the website will be transmitted to and stored by Google on servers in the United States. In case IP-anonymisation is activated on this website, your IP address will be truncated within the area of Member States of the European Union or other parties to the Agreement on the European Economic Area. Only in exceptional cases the whole IP address will be first transferred to a Google server in the USA and truncated there. The IP-anonymisation is active on this website. Google will use this information on behalf of the operator of this website for the purpose of evaluating your use of the website, compiling reports on website activity for website operators and providing them other services relating to website activity and internet usage. The IP-address, that your Browser conveys within the scope of Google Analytics, will not be associated with any other data held by Google. You may refuse the use of cookies by selecting the appropriate settings on your browser, however please note that if you do this you may not be able to use the full functionality of this website. You can also opt-out from being tracked by Google Analytics with effect for the future by downloading and installing Google Analytics Opt-out Browser Addon for your current web browser: https://tools.google.com/dlpage/gaoptout?hl=en.

Privacy policy
The personal information collected from the visitors of our website, including their identity, remains confidential. We respect the law(s) on confidentiality applicable to this website, hosted in Austria and we will never pass on these data to any third party, unless required by law.

No advertisment
Our website does not host any form of advertisement.

If you are interested in learning more about the SYMPATH project or collaborating scientifically with the SYMPATH project partners, the project coordinator welcomes your enquiries.

office@sympath-project.eu

 

SYMPATH PROJECT OFFICE

Dr Iris Grünert

biolution GmbH
Helmut-Qualtinger-Gasse 2/2
1030 Vienna, Austria

 

LEGAL NOTICE

The information on this site is subject to a disclaimer and a copyright notice.

LEGAL INFORMATION

LEGAL INFORMATION
Disclosure according to §5 ECG and §25 media law (Austria)
Please visit the WKO-Website

Publisher
AFFiRiS AG (Austria)

Basic direction
This web site provides information about the research project SYMPATH, which is funded by the European Union.  The mission of the website is to inform the general public and interested scientific community on background information of the project and progress of research as it becomes available. The information on the website is of a general nature and is not meant replace any advice or information provided by health care professionals.

HON Code certification
This site complies with the HONcode standard for trustworthy health information: verify here (https://www.healthonnet.org/HONcode/Conduct.html?HONConduct675866)

Important legal notice
The information on this site is subject to a disclaimer and a copyright notice.

 

COPYRIGHT NOTICE
All photographs copyright biolution GmbH unless otherwise stated. Photos must not be reproduced without permission of biolution GmbH or the copyright holder.

 

DISCLAIMER NOTICE
This web site contains information and files, individually and collectively the “information”, which is made available by SYMPATH and its publishers. All information is intended for internal use within the authorised website users. Our goal is to keep this information timely and accurate. If errors are brought to our attention, we will correct them as soon as possible. However, the publisher accepts no responsibility or liability whatsoever with regard to the material on this site. This material is: Information of a general nature only which is not intended to address the specific circumstances of any particular individual or entity. Not necessarily comprehensive, complete, accurate or up to date.

Please note that it cannot be guaranteed that a document available online exactly reproduces an officially adopted text, so that only European Union legislation published in the paper editions of the Official Journal of the European Communities is deemed authentic. It is our goal to minimise disruption due to technical errors. However, some data or information on our site may have been created or structured in files or formats that are not error-free and we cannot guarantee that our service will not be interrupted or otherwise affected by such problems. SYMPATH accepts no responsibility with regard to such problems, or the consequences thereof, incurred as a result of using this site. This disclaimer is not intended to contravene any requirements laid down in applicable national law nor to exclude liability for matters which may not be excluded under that law.

External links
This website provides links to websites which are considered helpful. These include national and international agencies and private organisations. We cannot confirm the accuracy of information provided by these websites. Links to a website does not constitute any endorsement by SYMPATH or its associates of the information or products presented on that website. Such websites are not within our control and may not follow the same privacy, security or accessibility policies. Once you visit such a website you are subject to the policies of that site. Links from the SYMPATH website to any other third-party website imply no endorsement by us of the website, company or product.

Use of google analytics / data privacy
This website uses Google Analytics, a web analytics service provided by Google, Inc. (“Google”). Google Analytics uses “cookies”, which are text files placed on your computer, to help the website analyse how users use the site. The information generated by the cookie about your use of the website will be transmitted to and stored by Google on servers in the United States. In case IP-anonymisation is activated on this website, your IP address will be truncated within the area of Member States of the European Union or other parties to the Agreement on the European Economic Area. Only in exceptional cases the whole IP address will be first transferred to a Google server in the USA and truncated there. The IP-anonymisation is active on this website. Google will use this information on behalf of the operator of this website for the purpose of evaluating your use of the website, compiling reports on website activity for website operators and providing them other services relating to website activity and internet usage. The IP-address, that your Browser conveys within the scope of Google Analytics, will not be associated with any other data held by Google. You may refuse the use of cookies by selecting the appropriate settings on your browser, however please note that if you do this you may not be able to use the full functionality of this website. You can also opt-out from being tracked by Google Analytics with effect for the future by downloading and installing Google Analytics Opt-out Browser Addon for your current web browser: https://tools.google.com/dlpage/gaoptout?hl=en.

Privacy policy
The personal information collected from the visitors of our website, including their identity, remains confidential. We respect the law(s) on confidentiality applicable to this website, hosted in Austria and we will never pass on these data to any third party, unless required by law.

No advertisment
Our website does not host any form of advertisement.

The EU project “SYMPATH” is a collaborative project of the Seventh Framework Programme of the European Union with the Grant Agreement No.: FP7-HEALTH-2013-1.3-3: 602999′

Little is known about the molecular processes, which affect a healthy brain during aging, but it is logical to assume the brain is no exception to this phenomenon.

Healthy individuals might have relatively low numbers of neurofibrillary tangles (red) throughout their brain.

Researchers believe that changes in the immune system represent a complex but important component of neurodegenerative diseases like Parkinson’s disease.

Neurodegenerative disorders constitute a major challenge to aging societies. Causal therapies have the greatest potential for alleviating the enormous burden these diseases pose by ensuring the brain can still perform its cognitive functions.

In synucleinopathies an imbalance between the rates of α-Synuclein synthesis and clearance can result in its misfolding and accumulation (red). This might favour the formation of toxic α-Synuclein aggregates leading to synaptic dysfunction.

Neurofibrillary tangles may be a target for immune cells (white), which might contribute to the disease through inflammatory responses.

Parkinson's disease and MSA affect neurons, which use the neurotransmitter dopamine.

The identification of α-Syn (red) as causative agent has constituted a significant advance in our understanding of synucleinopathies.

Targeting α-Syn (red) has become a rational choice for developing a causative therapy and moreover forms the basis for the clinical approach selected by the SYMPATH consortium.

Upon vaccination with α-Syn derived peptides (PD01 and PD03) dendritic cells (red) migrate to the lymphnodes presenting antigens to T cells (purple).

On the molecular level dendritic cells present small parts of antigen (red) on major histocompatibility complexes (MHC), which can be recognised by a matching T-cell receptor (TCR). This interaction generates through several other components (Lck/Fyn; ZAP 70) a signal to activate the T cell.

T cell activation is supported by regulatory interactions with B cells involving PD-1 and PDL-1 and CD40 and CD40L.

T cells differentiate into plasma cells, which produce antibodies. Patients vaccinated with PD01 and PD03 had antibodies recognising a-syn aggregates.

Neurofibrillary tangles of PD and MSA patients contain aggregates of a-Syn.

In vaccinated patients the neurofibrillary tangles would be marked by these antibodies for the immune system as pathological structures.

On the molecular level macrophages recognise pathological structures marked by antibodies by an interaction between Fc-receptor and the constant domain of the antibody.

Little is known about the molecular processes, which affect a healthy brain during aging, but it is logical to assume the brain is no exception to this phenomenon.

Healthy individuals might have relatively low numbers of neurofibrillary tangles (red) throughout their brain.

Researchers believe that changes in the immune system represent a complex but important component of neurodegenerative diseases like Parkinson’s disease.

Neurodegenerative disorders constitute a major challenge to aging societies. Causal therapies have the greatest potential for alleviating the enormous burden these diseases pose by ensuring the brain can still perform its cognitive functions.

In synucleinopathies an imbalance between the rates of α-Synuclein synthesis and clearance can result in its misfolding and accumulation (red). This might favour the formation of toxic α-Synuclein aggregates leading to synaptic dysfunction.

Neurofibrillary tangles may be a target for immune cells (white), which might contribute to the disease through inflammatory responses.

Parkinson's disease and MSA affect neurons, which use the neurotransmitter dopamine.

The identification of α-Syn (red) as causative agent has constituted a significant advance in our understanding of synucleinopathies.

Targeting α-Syn (red) has become a rational choice for developing a causative therapy and moreover forms the basis for the clinical approach selected by the SYMPATH consortium.

An immunotherapeutic approach targeting alpha-Synuclein could have the potential to slow down disease progression by activating dendritic cells and the immune system to eliminate neurofibrillary tangles in the brain.

Upon vaccination with α-Syn derived peptides (PD01 and PD03) dendritic cells (red) migrate to the lymphnodes presenting antigens to T-cells (purple).

On the molecular level dendritic cells present small parts of antigen (red) on major histocompatibility complexes (MHC), which can be recognised by a matching T-cell receptor (TCR). This interaction generates through several other components (Lck/Fyn; ZAP 70) a signal to activate the T-cell.

T-cell activation is supported by regulatory interactions with B-cells involving PD-1 and PDL-1 and CD40 and CD40L.

T cells differentiate into plasma cells, which produce antibodies. Patients vaccinated with PD01 and PD03 had antibodies recognising a-syn aggregates.

Neurofibrillary tangles of PD and MSA patients contain aggregates of a-Syn.

In vaccinated patients the neurofibrillary tangles would be marked by these antibodies for the immune system as pathological structures.

Little is known about the molecular processes, which affect a healthy brain during aging, but it is logical to assume the brain is no exception to this phenomenon.

Healthy individuals might have relatively low numbers of neurofibrillary tangles (red) throughout their brain.

Researchers believe that changes in the immune system represent a complex but important component of neurodegenerative diseases like Parkinson’s disease.

Neurodegenerative disorders constitute a major challenge to aging societies. Causal therapies have the greatest potential for alleviating the enormous burden these diseases pose by ensuring the brain can still perform its cognitive functions.

In synucleinopathies an imbalance between the rates of α-Synuclein synthesis and clearance can result in its misfolding and accumulation (red). This might favour the formation of toxic α-Synuclein aggregates leading to synaptic dysfunction.

Neurofibrillary tangles may be a target for immune cells (white), which might contribute to the disease through inflammatory responses.

Parkinson's disease and MSA affect neurons, which use the neurotransmitter dopamine.

The identification of α-Syn (red) as causative agent has constituted a significant advance in our understanding of synucleinopathies.

Targeting α-Syn (red) has become a rational choice for developing a causative therapy and moreover forms the basis for the clinical approach selected by the SYMPATH consortium.

An immunotherapeutic approach targeting alpha-Synuclein could have the potential to slow down disease progression by activating dendritic cells and the immune system to eliminate neurofibrillary tangles in the brain.

Upon vaccination with α-Syn derived peptides (PD01 and PD03) dendritic cells (red) migrate to the lymphnodes presenting antigens to T-cells (purple).

On the molecular level dendritic cells present small parts of antigen (red) on major histocompatibility complexes (MHC), which can be recognised by a matching T-cell receptor (TCR). This interaction generates through several other components (Lck/Fyn; ZAP 70) a signal to activate the T-cell.

T-cell activation is supported by regulatory interactions with B-cells involving PD-1 and PDL-1 and CD40 and CD40L.

T cells differentiate into plasma cells, which produce antibodies. Patients vaccinated with PD01 and PD03 had antibodies recognising a-syn aggregates.

Neurofibrillary tangles of PD and MSA patients contain aggregates of a-Syn.

In vaccinated patients the neurofibrillary tangles would be marked by these antibodies for the immune system as pathological structures.