Type 1 diabetes affects 17 million people globally and there is no cure; instead, patients must inject themselves with insulin daily and continually check their blood sugar levels to control their condition.
The goal of the INNODIA project is to advance our understanding of type 1 diabetes and address the lack of tools and technologies that will allow clinicians to predict, evaluate and prevent the onset and progression of type 1 diabetes. For patients, this would mean the ability to predict the rate at which their disease will progress. The project has set up a patient advisory committee (PAC) to ensure the work is in line with patients’ needs.
The knowledge and tools generated by the project have helped researchers in INNODIA and its sister project INNODIA HARVEST to optimise the design of four clinical trials of treatments for preventing and curing this debilitating disease. In 2020, trials started in children, adolescents and adults, who have been diagnosed with type one diabetes within the past 6 weeks and are aged from 5 to 45 years. All trials are running on the INNODIA Master Protocol, and the PAC is helping with recruitment for the trials.
Achievements & News
The INNODIA project is launching four diabetes drug studies, designed according to their regulator-approved master protocol
Diabetes projects INNODIA and INNODIA HARVEST have announced the winners of their Young Scientists Award. The award was open to all scientists under the age of 40 who are working in INNODIA and INNODIA HARVEST. ###Entrants were asked to explain the work they do in a one-minute video, and one of the most important requirements was the ability to explain their activities in lay language. The jury consisted of the patient advisory committee members.
The winner of the competition was Pieter-Jan Martens, a PhD student at KU Leuven in Belgium. In his winning video, he presents a study in which two potential diabetes treatments that work in different ways are combined. Research in mice suggests that the combination of both therapies is safe and 3-4 times more effective than either of the treatments on their own.
The project hopes that the award will encourage starting scientists to showcase their work and to name the challenges they face in diabetes research.
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Most research into autoimmune diseases focuses on the role of the immune system. But INNODIA research underscores the importance of studying the tissues under attack as well. ###Type 1 diabetes (T1D) occurs when the immune system attacks the beta cells in the pancreas. These cells are responsible for producing the hormone insulin, which regulates blood sugar levels. So far, research into autoimmune diseases has tended to focus more on the role of the immune system in driving the disease, and less on the role the target tissues (like the beta cells).
However, in research published in 2019, INNODIA researchers revealed major changes in gene activity levels in the beta cells. More recently, a new paper shows that as with diabetes, there are major gene activity changes in the target tissues of the other autoimmune diseases, such as the joints (rheumatoid arthritis), kidneys (systemic lupus erythematosus) and nerve cells (multiple sclerosis).
‘These observations suggest that future research on autoimmune diseases should focus on both the immune system and the target tissues, and on their dialog,’ the researchers conclude. ‘Discovering similar disease-specific signatures may allow the identification of key pathways that could be targeted for therapy, including the repurposing of drugs already in clinical use for other diseases.’
‘We must move away from the present “immune-centric-only” view of autoimmune diseases,’ explains the lead author of the paper, Professor Decio L. Eizirik of the Université Libre de Bruxelles. ‘Indeed, trying to understand these diseases focusing on the immune system only, and forgetting the target tissues, may be similar to attempting to fly a plane with only one wing.’
In summary, these papers show how results from an IMI project focusing on one disease area can have impacts in other disease areas.
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IMI’s INNODIA and INNODIA HARVEST projects have launched four clinical trials designed to test treatments to prevent and cure type 1 diabetes. The trials focus on children, adolescents and adults aged from 5 to 45 years who have been diagnosed within the past 6 weeks.###
The first trial, MELD-ATG, was launched by INNODIA in December 2020, and investigates whether ATG (anti-thymocyte globulin) antibodies targeting the immune system can stop the body´s immune system from attacking the cells in the pancreas that produce the hormone insulin. Insulin is responsible for regulating blood sugar levels. Three further clinical trials have since been launched by INNODIA’s sister project, INNODIA HARVEST. The trials all follow the INNODIA master protocol for clinical trials, which received the green light from the European Medicines Agency (EMA) earlier in 2020.
‘This is a very important moment for us,’ said INNODIA coordinator Professor Chantal Mathieu of University Hospital Leuven. ‘We bring our INNODIA network to the next level, by going from biomarker discovery to clinical interventions.’
All the trials focus on people who have just been diagnosed with type 1 diabetes because research has shown that in the newly-diagnosed, half of the cells in the pancreas that produce insulin are still working (this is known as the honeymoon). The hope is that by treating these people with drugs designed to protect these cells, they will retain the ability to produce their own insulin, and be spared the need to inject themselves with insulin.
‘With a strong community of people with type 1 diabetes and big pharma companies involved, we have high hopes to discover products that will increase the quality of life for people living with type one diabetes,’ said Dr Olivier Arnaud, a member of INNODIA’s Patient Advisory Committee (PAC).
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The INNODIA project is launching four diabetes drug studies, designed according to their regulator-approved master protocol.###
The project focuses on newly-diagnosed type 1 diabetes patients, as well as their close relatives, to understand the course of type 1 diabetes at the early stages of the disease. They want to know more about the rate of decline in insulin-producing beta-cells in the pancreas so that it can be detected, slowed, and even stopped.
This autumn, four clinical trials are due to get underway across Europe. They will be carried out by different clinical sites that form the network set up by INNODIA, and all sites will follow the 'Master Protocol' - guide documents for carrying out clinical trials - that was established by the project and green-lit this year by the European drugs regulator, the EMA. The participants in the trials will all have been diagnosed with diabetes in the preceding six weeks.
According to Veerle Vanhuyse, member of the INNODIA Patient Advisory Committee and communication representative for the project, using INNODIA’s Master Protocol makes participating in the clinical trials easier for study site personnel, as all manipulations, materials and communication channels are identical. “Patients will feel comfortable as they will see the familiar INNODIA study personnel and will receive information of the trials in similar formats as what has been used in the INNODIA natural history study. We are hitting the ground running.”
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The INNODIA project has developed a clinical trial master protocol, meaning launching new clinical trials for drugs to cure type 1 diabetes will be faster and easier. ###Before a clinical trial can start, the organisers have to submit the protocol of their study to regulatory authorities for approval. Preparing this protocol takes a lot of time.
To speed up the process, INNODIA has developed a master protocol for certain clinical trials of treatments that could potentially stop type 1 diabetes. ‘The idea of a master protocol is that rather than starting off with a new protocol every time you want to do one of these studies, you have a protocol that can be re-used for different studies – a recyclable protocol,’ explains David Dunger, of the University of Cambridge, who led INNODIA’s work on the master protocol. The basic design would always be the same, but what would change would be the annex describing the drug (or drugs) under investigation and the minor modifications needed to assess safety and efficacy.
The INNODIA clinical trial master protocol is specifically designed for phase 2 clinical trials of people who have just been diagnosed with type 1 diabetes. Most significantly, the European Medicines Agency (EMA) has given its green light to the master protocol, something that Professor Dunger describes as ‘a major step forward’. INNODIA is now set to use the protocol for its own clinical trials.
Patients play a central role in INNODIA’s work and Professor Dunger describes the Patient Advisory Committee’s work on the master protocol as ‘fantastic’. He also emphasises the benefits for patients of using a master protocol to set up clinical trials.
‘I think the message for the patients is that in the future we will see a very much better organised and timely way of doing studies, which will get more studies done, quicker, and coming up with the right drugs,’ he concludes.
An international team of scientists has identified the molecules that trigger the immune system in people with type 1 diabetes. The scientists hope that their findings will aid in the development of vaccines to prevent and treat the disease.### The work, funded in part by IMI through the INNODIA project, is published in the journal Cell Metabolism. Type 1 diabetes is an auto-immune disease. It occurs when immune cells called T lymphocytes attack the pancreatic beta cells, which are responsible for the production of the hormone insulin. To make up for the loss of these cells, people with type 1 diabetes have to inject themselves with insulin to manage their blood sugar levels. In this study, the researchers analysed the molecules on the surface of the pancreatic beta cells and how the T lymphocytes respond to them. They found that in both healthy people and diabetes patients, T lymphocytes recognised these molecules when they encountered them in the blood. However, in diabetes patients, the immune cells also recognised them in the pancreas. The team will use this new-found knowledge to develop vaccines to prevent and treat type 1 diabetes. However, while conventional vaccines seek to boost the immune response, the aim here will be to neutralise it.
Scientists from the IMI project INNODIA have shed new light on the role of white blood cells and the thymus in the development of type 1 diabetes. The work is published in the journal Science Immunology. ###Type 1 diabetes is an autoimmune disease that occurs when the immune system destroys the pancreatic beta cells responsible for producing insulin, the hormone that regulates blood sugar levels. The immune cells that attack the beta cells are a sub-group of white blood cells called CD8+ T lymphocytes. T lymphocytes are created in the bone marrow and pass through an organ called the thymus before entering the blood stream. Scientists thought that the thymus presented T lymphocytes with fragments of proteins similar to those found in the beta cells of the pancreas; T lymphocytes that recognise the beta cell protein fragments are destroyed. They also thought that in people with type 1 diabetes, this process does not work properly, and the thymus allows auto-immune T lymphocytes that respond to beta cells to pass into the blood stream. However, in this latest study, scientists found that these auto-immune CD8+ T lymphocytes are found in similar numbers in the blood of both healthy people and people with diabetes. However, the team did find higher levels of the T lymphocytes in the pancreas of people with diabetes. The team believes that healthy people may be able to control these auto-immune T lymphocytes thanks to regulatory T lymphocytes. People with diabetes may lack this ability to control the auto-immune T lymphocytes; furthermore, if their pancreas is inflamed, this may make the beta cells even more ‘visible’ to the autoimmune T cells.
The INNODIA project has recruited the first patient in a major clinical study of type 1 diabetes. The goal of INNODIA is to improve our understanding of type 1 diabetes and so pave the way for the development of novel treatments to prevent and cure it. In the new study, scientists will collect blood samples and data from people just diagnosed with type 1 diabetes and their relatives.### They will then follow the evolution of the disease in the study participants. ‘This way we will be able to better understand the relationship between changes in beta cell function, immune profiles, genetic and environmental factors and their role in the onset of the disease,’ says INNODIA coordinator Chantal Mathieu of the University of Leuven in Belgium. Patients were heavily involved in the design of the study. ‘Listening to the patient’s voice and following their advice was crucial in setting up this effort,’ said Olivier Arnaud of JDRF International. Looking to the future, the project will open further study centres in Europe, giving more patients the opportunity to take part. In a video, diabetes patient and INNODIA Patient Advisory Committee member Kyle Rose explains: ‘These [studies] are what are going to allow new therapies, new drugs to be developed so that we can all lead healthier lives as people with diabetes. It can really make a difference.’
INNODIA video follows the journey of a blood sample through the projectIn 2019, IMI launched a contest among its projects to create a short, simple mobile video. The winning entry came from diabetes project INNODIA. Through the video, viewers meet the scientists involved in the project and follow the journey of a blood sample as the team processes and analyses it in their quest to learn more about type 1 diabetes. ###The video shows a sample arriving at one of the project’s laboratories where the white blood cells are extracted and subjected to tests that reveal the white blood cells involved in diabetes. The results are entered in a database along with results from other labs across Europe. Meanwhile, cells not needed for the initial experiment are stored for future use.
ParticipantsShow participants on map
- Eli Lilly And Company LTD, Basingstoke, United Kingdom
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Imcyse SA, Sart Tilman, Belgium
- Novo Nordisk A/S, Bagsvaerd, Denmark
- Sanofi-Aventis Deutschland GMBH, Frankfurt / Main, Germany
Universities, research organisations, public bodies, non-profit groups
- Academisch Ziekenhuis Leiden, Leiden, Netherlands
- Cardiff University, Cardiff, United Kingdom
- Centre Hospitalier De Luxembourg, Luxembourg, Luxembourg
- Hannoversche Kinderheilanstalt, Hannover, Germany
- Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt GMBH, Neuherberg, Germany
- Institut National De La Sante Et De La Recherche Medicale, Paris, France
- Katholieke Universiteit Leuven, Leuven, Belgium
- King'S College London, London, United Kingdom
- Kobenhavns Universitet, Copenhagen, Denmark
- Lunds Universitet, Lund, Sweden
- Medizinische Universitat Graz, Graz, Austria
- Oslo Universitetssykehus Hf, Oslo, Norway
- Ospedale Pediatrico Bambino Gesu, Rome, Italy
- Oulun Yliopisto, Oulu, Finland
- Region Hovedstaden, Hilleroed, Denmark
- Slaski Uniwersytet Medyczny W Katowicach, Katowice, Poland
- Stichting Radboud Universitair Medisch Centrum, Nijmegen, Netherlands
- Technische Universitaet Dresden, Dresden, Germany
- The University Of Exeter, Exeter, United Kingdom
- Universita Degli Studi Di Siena, Siena, Italy
- Universita Degli Studi Gabriele D'Annunzio Di Chieti-Pescara, Chieti, Italy
- Universita Di Pisa, Pisa, Italy
- Universita Vita-Salute San Raffaele, Milano, Italy
- Universitaet Ulm, Ulm, Germany
- Universite De Lausanne, Lausanne, Switzerland
- University of Cambridge, Cambridge, United Kingdom
- University of Helsinki, University of Helsinki, Helsinki, Finland
- University of Oxford, Oxford, United Kingdom
- University of Turku, Turku, Finland
- Université Libre de Bruxelles, Bruxelles, Belgium
- Univerza V Ljubljani, Ljubljana, Slovenia
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
- Human Cell Design, Toulouse, France
- Jdrf International, New York, United States
- The Leona M. And Harry B. Helmsley Charitable Trust, New York, United States
Non EFPIA companies
- Novartis Pharma AG, Basel, Switzerland
|Name||IHI funding in €|
|Academisch Ziekenhuis Leiden||542 245|
|Cardiff University||384 316|
|Centre Hospitalier De Luxembourg||284 650|
|Hannoversche Kinderheilanstalt||645 830|
|Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt GMBH||362 276|
|Human Cell Design||373 878|
|Institut National De La Sante Et De La Recherche Medicale||1 866 870|
|Katholieke Universiteit Leuven||1 302 643|
|King'S College London||348 617|
|Kobenhavns Universitet||1 060 600|
|Lunds Universitet||136 850|
|Medizinische Universitat Graz||352 526|
|Oslo Universitetssykehus Hf||422 401|
|Ospedale Pediatrico Bambino Gesu||157 050|
|Oulun Yliopisto||431 700|
|Region Hovedstaden||995 063|
|Slaski Uniwersytet Medyczny W Katowicach||291 200|
|Stichting Radboud Universitair Medisch Centrum||56 023|
|Stichting Radboud Universiteit (left the project)||367 532|
|Technische Universitaet Dresden||1 160 045|
|The University Of Exeter||50 000|
|United Kingdom Research And Innovation (left the project)||19 423|
|Universita Degli Studi Di Siena||726 497|
|Universita Degli Studi Gabriele D'Annunzio Di Chieti-Pescara||46 404|
|Universita Di Pisa||455 066|
|Universita Vita-Salute San Raffaele||130 540|
|Universitaet Ulm||281 380|
|Universitetet I Oslo (left the project)||3 763|
|University of Cambridge||1 945 739|
|University of Helsinki||800 561|
|University of Oxford||111 000|
|University of Turku||572 050|
|Université Libre de Bruxelles||657 905|
|Univerza V Ljubljani||287 358|
|Total Cost||17 630 001|