SYMPATH aims to advance curative therapy for α-Synucleinopathies:
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.
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
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
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
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.
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.
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.
PROSPECTS FOR PD03 VACCINE IN PHASE II DESIGN
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.
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.
Currently 6 research reports have been published within SYMPATH, and there are more to come!
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.
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
“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,
“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
“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
“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
“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
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.
SYMPATH PROJECT OFFICE
Dr Iris Grünert
1030 Vienna, Austria
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