AETIONOMY

Organising mechanistic knowledge about neurodegenerative diseases for the improvement of drug development and therapy
AETIONOMY logo

FACTS & FIGURES

Start Date
End Date
Call
IMI1 - Call 8
Grant agreement number
115568

Type of Action: 
RIA (Research and Innovation Action)

Contributions
IMI Funding
7 993 234
EFPIA in kind
8 021 460
Other
1 797 522
Total Cost
17 812 216

Summary

Today, diseases are defined largely on the basis of their symptoms. Yet, while two patients may share the same diagnosis, the underlying causes of their symptoms may be very different. This means that a treatment that works in one patient may prove ineffective in another. There was a broad recognition that a new approach to disease classification is needed. The AETIONOMY project has paved the way for a new approach to the classification of neurodegenerative diseases, particularly Alzheimer’s and Parkinson’s diseases, which will lead to better drugs and increased chance that patients will receive a treatment that works for them.

Key achievements

The AETIONOMY project

  • recruited more than 400 PD patients and generated a unique biobank with clinical data and bio samples for further analyses;
  • developed the first version of a mechanism-based taxonomy for Alzheimerism and Parkinsonism;
  • generated 8 biomarkers;
  • successfully developed strategies and new algorithms to associate mechanisms with biomarkers (and progression) in patient-level data;
  • generated a publicly accessible resource, the AETIONOMY Knowledge Base (AKB), that contains high-quality, curated data, and computable models of disease;
  • created the largest inventory of computable disease mechanisms underlying neurodegeneration worldwide, NeuroMMSig, (Alzheimerism=126, Parkinsonism=76, Epilepsy=31);
  • worked on the  concept of Virtual Dementia Cohorts for effective data sharing.

Background

Dementia affects 44 million people globally, and that figure is set to rise to 135 million by 2050, mostly due to ageing of the population. Alzheimer’s disease is the most common form of dementia, accounting for between 60% and 80% of all cases. Meanwhile an estimated 4-6 million people globally suffer from Parkinson’s disease. There is no cure for these devastating diseases, and caring for patients as their disease progresses represents an immense burden for family members, carers, and health and social care systems.

Developing new treatments for brain disorders takes longer and costs more than for other disease areas. When it comes to Alzheimer’s and Parkinson’s diseases, the way these diseases are classified is hampering efforts to develop effective, targeted treatments.

Currently, diseases are defined largely on the basis of the patient’s symptoms and where they occur in the body. Many are classified based simply on the name of the doctor or researcher who first discovered or described the disease – this is the case for both (Alois) Alzheimer’s and (James) Parkinson’s diseases.

Rethinking classification: from effect to cause

There is growing evidence that while two patients may be classified as having the same disease, the genetic or molecular causes of their symptoms may be very different. This means that a treatment that works in one patient will prove ineffective in another. In other cases, diseases that are currently defined as separate conditions may share a common molecular basis. There is therefore now broad recognition that the way diseases are classified needs to change, and the field of neurodegenerative diseases in particular is considered to be ripe for a rethink.

AETIONOMY was an ambitious project: there are few meaningful correlations or causal links between disease features at the molecular level (e.g. genetic mutations or gene activity), features at the tissue / organ level (e.g. changes in the brain), and features at the clinical level (including symptoms and the results of imaging scans). Even in cases where the disease runs in families, it is not uncommon to find family members who share the same genetic mutation but have different clinical symptoms. For most patients, the disease is simply described as ‘idiopathic’, meaning the cause is unknown.

Nevertheless, the literature, public databases, and private companies have vast amounts of data that could be used to pave the way for a better classification of patients, based on underlying causes instead of symptoms. However, we lack an efficient way to generate new knowledge from these resources, and that is where the AETIONOMY project comes in.

The AETIONOMY team tackled the problem of how to dynamically organise and structure different types of data (ranging from molecular data to information on symptoms) and how to apply this knowledge to construct a new classification of patient groups based on the underlying causes of their disease. Achieving this is far beyond the scope of any single company or university; the key to AETIONOMY’s success is the broad nature of the project consortium, which brought together pharmaceutical companies, universities, and two patient groups, and boasts expertise in neurodegenerative diseases, molecular biology, clinical research, research ethics, data modelling and simulation, data standards, and patient involvement in research.

The new project delivered data, tools and recommendations that can be used by the biomedical community and regulators to develop and approve new treatments and diagnostic tests.

An urgent need for new treatments

There are currently no drugs capable of curing Alzheimer’s or Parkinson’s diseases, and the few treatments designed to alleviate symptoms are not effective in all patients. By identifying sub-groups of patients based on the underlying, molecular cause of their disease, AETIONOMY will usher in a new era of personalised medicine, in which patients’ treatments will be determined on the basis of the cause of their disease, not its effects.

Achievements & News

Alzheimer's researchers use AI to get access to brains
December 2019

IMI’s AETIONOMY project used digital technology to simulate 'personalised' brains with individual 'wiring', allowing them to study processes associated with Alzheimer's. ‘How do we overcome the challenge of the inaccessibility of the human brain?’ asks to Professor Martin Hofmann-Apitius, academic lead of AETIONOMY, in an interview ###with the IMI Programme Office. ‘Actually, in-silico technologies help us to understand what is going on in the brain even before we can measure it directly by taking samples from living people.’ The AETIONOMY project used digital technology to study brains without needing samples from living people, allowing them to simulate processes associated with Alzheimer's. In their mission to establish new ways of reclassifying Alzheimer’s and other neurodegenerative diseases, the team tackled the problem of how to obtain, organise, structure, integrate and interpret a broad range of distinct types of data, ranging from molecular data, to information on symptoms, available across the neurodegeneration community. They brought new structure to the classification of disease by dissecting the underlying mechanistic and molecular causes of disease, and by linking these to clinical evidence to attempt to partially validate a selection of these mechanistic drivers.

‘Humans like reductionist approaches - one cause, one reason. But there is reason to believe there are many causes of Alzheimer’s disease that may work in combination, and that was one of the biggest scientific challenges in AETIONOMY: the combinatorial causality, Professor Hofmann-Apitius concludes. ‘The task of AETIONOMY was to unravel this and I expect to see impact of our findings at least ten years down the line.’

Read more

IMI projects feature in new brochure on the brain and digital technologies
June 2019

IMI projects are among those featured in a new brochure on how the digital revolution is transforming EU-funded brain research. The brochure, produced by CORDIS, was published to coincide with IMI’s Stakeholder Forum on the same subject. The IMI projects featured are AETIONOMY, EU-AIMS and PRISM. AETIONOMY systematically captures and represents knowledge on neurodegenerative diseases in a computable format that represents causes and effects and that can be analysed using algorithms. EU-AIMS has developed a large autism database, one of the richest of its kind in the world, which has the potential to drastically change the knowledge base for autism. Finally, PRISM has developed a new framework that would help researchers better understand the complexity of neuropsychiatric illness, moving away from current reductive disease classifications, to pave the way for new treatments.

IMI projects working on a new way of defining diseases
February 2015

The work of IMI’s PRECISESADS and AETIONOMY projects on disease taxonomy is spotlighted in a new Nature Reviews Discovery comment piece.### Currently, most diseases are still defined largely on the basis of their symptoms, yet while two patients may share the same diagnosis, the underlying causes of their symptoms may be very different. This means that a treatment that works in one patient may prove ineffective in another. The AETIONOMY and PRECISESADS projects are pioneering a new approach to the classification of disease; for AETIONOMY, in the field of Alzheimer’s and Parkinson’s diseases, and for PRECISESADS, in the field of systemic autoimmune diseases (such as rheumatoid arthritis and lupus). Although the projects are tackling the problem in different ways, their overall goal is the same: to pave the way towards a new taxonomy of disease that is based on the underlying causes of disease. In the long term, this will help to diagnose patients more accurately and provide them with a treatment that works for them.

IMI scientist wins entrepreneurship award
February 2014

The 2013 award for Hungarian Young Entrepreneur of the Year was won by Tamas Letoha, Chief Executive Officer of Pharmacoidea, which is a partner in two IMI projects.### Tamas was selected as the winner from over 400 public nominations from more than 50 small and medium-sized enterprises (SMEs) from a number of different business sectors. Dr Letoha, a medical researcher by training, received his award from the Hungarian Prime Minister, Viktor Orbán at the Role Model of the Year Award gala in January. The annual award is sponsored by the Role Model Foundation which was set up in 2013 to recognise successful Hungarian entrepreneurs under the age of 40. Tamas heads up Pharmacoidea Ltd. which specialises in R&D in drug discovery, functional food development and experimental cellular therapeutics against carcinomas.  Pharmacoidea is a partner in two IMI projects, COMPACT and AETIONOMY. Tamas said that his achievements ‘were pretty much due to international R&D projects like AETIONOMY ’ and that he highly valued his connections with IMI.

Participants Show participants on map

EFPIA companies
  • Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
  • Novartis Pharma AG, Basel, Switzerland
  • Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
  • UCB Biopharma SRL, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
  • Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain
  • Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
  • Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forschung E.V., München, Germany
  • Fundacio Barcelonabeta Brain Research Center, Barcelona, Spain
  • Gottfried Wilhelm Leibniz Universitaet Hannover, Hannover, Germany
  • Institut Du Cerveau Et De La Moelle Epiniere, Paris, France
  • Karolinska Institutet, Stockholm, Sweden
  • Universitatsklinikum Bonn, Bonn, Germany
  • Universite D'Aix Marseille, Marseille, France
  • Universite Du Luxembourg, Esch-sur-Alzette, Luxembourg
Small and medium-sized enterprises (SMEs)
  • Pharmacoidea Fejleszto Es Szolgaltato Kft, Szeged, Hungary
Patient organisations
  • Alzheimer Europe, Luxembourg, Luxembourg
Third parties
  • Institut National De La Sante Et De La Recherche Medicale, Paris, France

CONTACT

Project coordinator
Phil Scordis
UCB Biopharma SPRL
United Kingdom
+44 1753 777187
Phil.Scordis[at]ucb.com
Managing entity
Martin Hofmann-Apitius
Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.
martin.hofmann-apitius[at]scai.fraunhofer.de