Reach α-Synuclein mediated pathology


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



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.


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


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



Eight excellent partners in three countries advised by outstanding experts

Mag. Vera Bürger

Dr Iris Grünert
biolution GmbH

Prof. Wassilios Meissner
CHU Bordeaux 

Claire Levy Marchal, MD,MSc

Prof. Dr Werner Poewe
Medical University of Innsbruck

Prof. Dr Dieter Willbold
Forschungszentrum Jülich GmbH

Prof. Olivier Rascol
University Hospital

We Target Parkinson’s Disease and MSA

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

Parkinson’s disease

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


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

Parkinson’s 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 sense of smell and 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.


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

MSA progresses rapidly leading to death of the affected individual within 9 years. 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.


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.


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

Partner 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.


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



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 a surface-based fluorescence intensity distribution analysis (sFIDA) for quantitative analysis of aggregated α-Syn. It enables assessing 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.




Results of this study – favorable safety profile of the PD03 vaccine and the immune response versus α-Syn epitope undoubtedly support further development of this compound in a phase II design with dose levels that are expected to meaningfully reduce pathogenic α-Synuclein in the brain of patients suffering with Parkinson’s disease.



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.




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.



Dedicated events in collaboration with patient organisations as well as researchers


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

View all publications

Multiple System Atrophy – State of the Art.
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.
Herrmann et al., 2017
D.O.I 10.1016/j.cca.2017.01.010

Active immunization therapies for Parkinson’s disease and multiple system atrophy.
Schneeberger et al., 2016
D.O.I. 10.1002/mds.26377

Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations.
Dehay et al., 2015
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.
Mandler et al., 2015
D.O.I. 10.1186/s13024-015-0008-9

Targeting α-synuclein: Therapeutic options.
Dehay et al., 2015
D.O.I. 10.1002/mds.26568


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


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.



© 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.




© 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 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 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.


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.



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


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


“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


“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

“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

“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


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.




Dr Iris Grünert

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



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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.

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 alpha-Synuclein synthesis and clearance can result in its misfolding and accumulation (red). This might favour the formation of toxic alpha-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 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 a-syn derived peptides (PD01 and PD03) dendritic cells (red) migrate to the lymphnodes presenting antigens to T-cells (purple).

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