NAIMIT

Natural immunomodulators as novel immunotherapies for type 1 diabetes

NAIMIT End-Meeting, 31th October 2014 – Leuven, Belgium Location: Pentalfa, O&N1, UZ-Gasthuisberg, Leuven

Posted on | September 16, 2014 | Comments Off

 

Attendance is free, but please register by sending an e-mail to Lut.Overbergh@med.kuleuven.be to confirm your participation, since places are limited.

Download as pdfNAIMIT Program Leuven 31 10 2014

10.00 – 10.30       Arrival and welcome coffee

10.30 – 10.45       State of the Moment on NAIMIT – Chantal Mathieu

10.45– 11.35        WP1 – Re-educating antigen-presenting cells – Chair B. Roep
Bart Roep (LUMC): Tolerogenic dendritic cells to treat type 1 diabetes: what have we learned in NAIMIT

Jaap Jan Zwaginga (LUMC):Clinical translation and assessment of tolerogenic DCs in a first-in-man trial

11.35– 12.50           WP2 – Restoring the T-cell balance – Chair M. Peakman

Vivienne Gibson (KCL): Development of novel antigen-specific immunotherapy by the NAIMIT Consortium

Colin Dayan (CU): Using the skin as an immunotherapeutic adjuvant

Jocelyne Demengeot (FCG-IGC): Correcting T cell selection at the source

12.50 – 14.30 Lunch for all attendees

14.30– 14.55 WP3 – TCR-directed immunotherapy – Chair C. Mathieu

Stephen Megit (IMC): TCR-directed immunotherapy in type 1 diabetes

14.55– 15.45 WP4 – Mucosal intervention for tolerance restoration – Chair F. Dotta

ConnyGysemans (KUL): Genetically modified L.lactis and immunomodulation in autoimmune diabetes

Guido Sebastiani (UNISI): Islet inflammation and microRNA signatures in NOD mice treated with genetically modified L.lactis

15.45 – 16.15 coffee break

16.15– 17.05 WP5 – Dangerous Liaisons – Pancreatic beta cells and the immune system in type 1 diabetes – Chair D.Eizirik
Decio Eizirik (ULB): The crosstalk between candidate genes for type 1 diabetes, innate immunity and the gene networks regulating beta cell apoptosis

Dieter Rondas (KUL): Dialogue between the beta cell and the immune system: Role for GRP78

17.05 – 17.30 WP6 – Pharmacogenetics: towards individualised therapies – Chair K. Badenhoop
Klaus Badenhoop: Predicting the immune response to vitamin D and steroids in type 1diabetes

17.30 – 17.45 NAIMIT, final moments

17.45 – Reception for all attendees

NAIMIT Annual Meeting, 29th October 2013 – Portugal

Posted on | October 21, 2013 | Comments Off

Tuesday 29 Oct 2012 open meeting

Location: Instituto Gulbenkian de Ciência,

Rua da Quinta Grande, Oeiras

Room: The Ionians. Average 45mn per WP

08:30 – 09:00 Welcome coffee and registration externals participants

09:00 – 09:15 State of the Moment on NAIMIT – Chantal Mathieu

09:15 – 10:15 WP1 Re-educating antigen-presenting cells – Chair Bart Roep
Bart Roep (LUMC): Re-educating antigen-presenting cells: Overview (25 min + 10 min disc)
Tanja Nikolic (LUMC): Clinical translation of vitaminD3/Dex modulated tolerogenic DCs. (15 min + 10 min disc)

10:15 – 11:15 WP2 Restoring T-cell balance – Chair Mark Peakman
Vivienne Gibson (KCL). Multi-peptide immunotherapy for T1D. (20 min + 10 min disc)
Colin Dayan (CU). Experience from multi-centre early phase study of peptide therapy in T1D. (20 + 10 min disc)

11:15 – 11:30 Coffee break

11:30 – 12:15 WP3 TCR-directed immunotherapy – Chair Chantal Mathieu
Stephen Megit (IMC): Summary of Immunocore technology – including Autoimmunity program (35 min + 10 min disc)

12:15 – 13:45 Lunch break

13:45 – 14:30 WP4 Mucosal intervention for tolerance restoration – Chair Francesco Dotta
Chantal Mathieu (KUL): L. lactis in type 1 diabetes: What we learned from mice (35 min + 10 min disc).

14:30 – 15:15 WP5 Beta-cell protection and restoration: dialogue with the immune system – Chair Decio Eizirik
Decio Eizirik (ULB): Beta-cell protection and restoration: dialogue with the immune system (35 min + 10 min disc)

15:15 – 15:30 Coffee break

15:30 – 16:00 WP6 Pharmacogenetics: towards individualized therapies – Chair Klaus Badenhoop
Klaus Badenhoop (GUF): Update on pharmacogenetics of immunomodulation. (20-25min + 10 min disc)

16:00 – 16:40 Harmonizing clinical trials within NAIMIT – Polly Bingley (30 min + 10 min disc)

16:40 – 17:10 NAIMIT: The future – Chantal Mathieu

17:10 – 18:00 Outdoor (tent): Discussion between PhDs and post-docs NAIMIT with external participants (posters)

19:30 Diner at Oba, Cascais.
Return to hotel by private bus

Attendance is free of charge, but please send an email to lut.overbergh@med.kuleuven.be to confirm your participation.

Partner Presentation

Posted on | October 1, 2013 | Comments Off

Prof. Chantal Mathieu presents NAIMIT

Posted on | May 4, 2013 | Comments Off

EU Opendoors event

Posted on | May 1, 2013 | Comments Off

The NAIMIT project will be presented at the Europe Day 2013 where you can discover the concrete actions of the European Commission .

Please come and visit our NAIMIT stand on May 4th from 10 am till 6 pm, Berlaymont building, Brussels.

Press Release: ActoGeniX closes EUR 10.7 million financing round

Posted on | April 22, 2013 | Comments Off

Ghent, Belgium – April 18th, 2013

ActoGeniX, a clinical stage biopharmaceutical company, successfully closed a Series B equity financing round, raising EUR 10.7 million (USD 14 million). This financing round was led by new investor Saffelberg Investments (Belgium). ActoGeniX’s founders and current investors all participated in this transaction, thus confirming their commitment to the strategic roadmap.

This financing round will allow ActoGeniX to execute its business strategy and fund ongoing and planned development programs.

ActoGeniX focuses on the development and commercialization of ActoBiotics™, a novel class of orally administered and locally acting biopharmaceuticals. ActoBiotics™ represent a novel concept for oral administration of therapeutic proteins, and are designed to be safer and more effective than injectable biopharmaceuticals.
ActoGeniX is developing ActoBiotics™ in mucosal and immune diseases such as oral mucositis, inflammatory bowel disease, celiac disease, and type 1 diabetes.

Dr. Bernard Coulie, CEO of ActoGeniX, comments: “We are delighted with this financing, accomplished in a challenging market environment. It provides ActoGeniX with sufficient funding to execute its ambitious business plan. It will enable us to progress our pipeline including bringing key products to clinical proof of concept.”

Dr. Staf Van Reet, Chairman of the Board of ActoGeniX, adds: “To have raised such a substantial amount of new equity capital during these times is a clear vote of confidence in ActoGeniX´s promising platform and pipeline. It provides ActoGeniX with a far stronger position when presenting its platform and pipeline to potential pharma partners.”

FULL PRESS RELEASE IN PDF :

Press release Actogenix 18 April 2013.pdf

Prof. Chantal Mathieu receives prestigious “InBev-Baillet Latour Prize” for clinical research 2013

Posted on | April 22, 2013 | Comments Off

THE INBEV-BAILLET LATOUR FUND AWARDS THE PRIZES FOR CLINICAL RESEARCH 2013 TO PROFESSORS LAURENCE BOON AND MIIKKA VIKKULA (UCL) AND TO PROFESSOR CHANTAL MATHIEU (KU LEUVEN)

Since 2007, the InBev-Baillet Latour Fund has awarded the Prize for Clinical Research to young Belgian researchers, from Flanders and Wallonia, in order to promote clinical research in Belgium. This year’s prizes were awarded to Professors Laurence Boon and Miikka Vikkula (UCL) and to Professor Chantal Mathieu (KU Leuven). The Prizewinners were selected by the juries for their groundbreaking and high-quality scientific research in the fields of vascular anomalies and diabetes, respectively.

Download pdf :

Press Release- Prize Clinical Research 2013-InBev-Baillet Latour.pdf

NAIMIT Annual Meeting, 29 October 2012 – Pisa, Italy

Posted on | October 22, 2012 | No Comments

NAIMIT Annual Meeting, 29 October 2012 – Pisa, Italy
Location: L’Abitalia Tower Plaza, Pisa

Program

9.00 – 9.30 Arrival and welcome coffee

9.30 – 10.00 State of the Moment on NAIMIT – Chantal Mathieu

10.00 – 10.45 WP1 – Educators re-educated – Tolerogenic DCs induce functionally distinct subtypes of Tregs
By Bart Roep
(30min talk + 15min discussion)

10.45 – 11.00 Coffee break

11.00 – 11.45 WP2 – Progress in antigen-specific immunotherapy with peptides
By Mark Peakman
(30min talk + 15min discussion)

11.45 – 12.30 WP3 – Summary of Immunocore technology – including Diabetes program
By Stephen Megit
(30min talk + 15min discussion)

12.30 – 13.30 Lunch break

13.30 – 14.15 WP4 – The Lactococcus tool for intervention in Type 1 Diabetes
By Chantal Mathieu
(30min talk + 15min discussion)

14.15 – 15.00 WP5 – The role of alternative splicing in the dialogue between beta cells and the immune system in early type 1 diabetes
By Decio Eizirik
(30min talk + 15min discussion)

15.00 – 15.45 WP6 – Genetically guided personalized medicine (GPM): diagnostic steps and stratification for vitamin D/glucocorticoid action for type 1 diabetes immune modulation
By Klaus Badenhoop
(30min talk + 15min discussion)

Attendance is free, but please send an e-mail to lut.overbergh@med.kuleuven.be to confirm your participation

Press release : Reversal of Type 1 diabetes through restoration of immune tolerance via the gut

Posted on | April 12, 2012 | No Comments

Type 1 diabetes melllitus (T1DM) is an autoimmune disease characterised by immune-mediated destruction of insulin-producing beta-cells in the pancreas. The incidence of T1DM in childhood is increasing at about 3% per year. T1DM is the most common metabolic disease in the young. In Europe, about two million people (around 0.5 % of the population) and several million people world-wide suffer from this disease. At present, T1DM cannot be prevented or arrested in its course and lifelong insulin therapy is needed for survival. Still, chronic complications, such as eye disease, kidney disease and vascular disease, affect lifespan and in particular quality of life. Since it carries such a significant chronic disease burden, T1DM has become a major public health concern worldwide, emphasizing the urgent need for safe and effective intervention and prevention strategies.

The true cause of T1DM remains elusive, but an autoimmune destruction of the insulin-producing beta-cell in the pancreas lies at the basis and finding ways to interfere with this immune system, aimed as restoring tolerance in a specific way towards the beta-cell without interfering with the immune defences of the subject opens the way for prevention of this disease. To date, several interventions have been assessed in patients with T1DM and treatment with antibodies directed against a marker of T lymphocytes, anti-CD3, have been the most promising. However, till now, solid evidence on the applicability of this intervention in a safe and acceptable way in patients is lacking.

The group at the University of Leuven (KU Leuven) has been involved in studies on prevention and intervention in T1DM, extending from bench to bedside. Prof. C. Mathieu leads a basic science laboratory specialised in in vitro studies and animal models of type 1 diabetes, and is head of the clinical Endocrinology department, where over 1000 patients with T1DM are being treated. In that clinical department, several clinical studies on diabetes therapies are currently taking place.

The laboratory is part of several research networks, funded by national and international agencies, amongst which the JDRF (Juvenile Diabetes Research Foundation), FWO (Fonds Wetenschappelijk Onderzoek Vlaanderen), and the European Commission. The latter supports a network on Immune Intervention in T1DM (NAIMIT), in the context of Framwork 7.

The work published on April 9th in the Journal of Clinical Investigation, is the fruit of a collaboration of several groups within the NAIMIT consortium, amongst which the company Actogenix, inventors of ActobioticTM, live biologically-contained genetically-modified Lactococcus lactis, able to deliver proteins and peptides of choice in the gut. The paper reports on the ability of ActoBioticTM (which secrete both the auto-antigen pro-insulin and the immune-modulatory cytokine interleukin-10 (IL-10), to arrest progression of diabetes in an animal model of T1DM, when administered in combination with a low dose of anti-CD3 antibody (5 days). When newly diagnosed, overtly diabetic NOD mice were treated with this regimen, a stable remission could be induced, lasting stably for weeks after therapy was interrupted. Extensive immune phenotyping of the mice revealed increased local regulatory T-cell frequencies which not only accumulated in the pancreatic islets, but also suppressed in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, arguing against excessive immunosuppression.
Considering the fact that these findings report on reversal of overt diabetes, without immune suppression, but with restoration of antigen-specific tolerance via the gut, these findings are of the utmost clinical relevance, as translation to the human setting is easily realizable.

NAIMIT Annual Meeting – 7 November 2011 – Leiden, The Netherlands

Posted on | September 2, 2011 | No Comments

Program

NAIMIT Annual Meeting – 7 November 2011 – Leiden, The Netherlands

Location:

Kasteel Oud-Poelgeest
Poelgeesterweg 1, 2341 NM Oegstgeest
, Leiden, The Netherlands

10.30 – 11.00 Arrival and welcome coffee

11.00 – 11.35 Jay Skyler – State of the art lecture on Clinical Prevention and Intervention Studies in Type 1 Diabetes

11.35 – 12.00 State of the Moment on NAIMIT – Chantal Mathieu

12.00 – 13.00 Lunch break

13.00 – 13.45 WP1 – Re-educating antigen-presenting cells
Introduction by WPL Bart Roep

Bart Roep: Tolerogenic Dendritic Cell Therapy
(25min talk + discussion)

13.45 – 14.30 WP2 – Restoring the T-cell balance
Introduction by WPL Mark Peakman

Mark Peakman: Towards T-cell tolerance
(25min talk + discussion)

14.30 – 14.50 Ezio Bonifacio: Update on FP7– DIAprepp

14.50 – 15.35 WP3 – TCR-directed immunotherapy
Introduction by WPL Chantal Mathieu

Rebecca Ashfield: ImmTAC technology applied to Cancer and Diabetes
(25min talk + discussion)

15.35 – 15.50 coffee break

15.50 – 16.35 WP4 – Mucosal intervention for tolerance restoration
Introduction by WPL Francesco Dotta

Pieter Rottiers: Mucosal tolerance induction with genetically engineered Lactococcus lactis
(25min talk + discussion)

16.35 – 16.55 Mikael Knip: DIABIMMUNE: Testing the hygiene hypothesis in type 1
diabetes and other immune-mediated diseases

16.55 – 17.40 WP5 – Beta-cell protection and restoration: dialogue with the immune
system. Introduction by WPL Decio Eizirik

Decio Eizirik: The beta-cell, more than a target in type 1 diabetes
(25min talk + discussion)

17.40 – 18.25 WP6 – Pharmacogenetics: towards individualised therapies.
Introduction by WPL Klaus Badenhoop

John Todd: Understanding genes- towards personalized medicine
(25min talk + discussion)

NAIMIT Annual Meeting – 22 – 24 November 2010 – Hannover, Germany

Posted on | November 20, 2010 | No Comments

Program

Monday 22 Nov 2010

12.00- 14.00 Arrival/Welcome – Lunch Buffet

Training Session – Part 1

14.30 – 15.30 Invited Speaker
G Breves (TiHo, Hannover),
Title: Probiotics as immunomodulatory agents and the function of the intestinal tract

15.30 – 15.45 Coffee Break

WP5 – Beta-cell protection and restoration: Dialogue with the immune system – WP leader DL Eizirik

15.45 – 15.50 DL Eizirik (ULB, Brussels) – Overview
15.50 – 16.10 F Moore (ULB, Brussels)
Title: The gene networks regulating STAT-1/IRF-1-induced insulitis
16.10 – 16.25 L Overbergh (KUL, Leuven)
Title: Gene networks modulated by cytokines and vitamin D in mice
16.25 – 16.40 F Dotta (UNISI, Siena)
Title: Islet regeneration
16.40 – 16.55 S Lenzen (MHH, Hannover)
Title: Diabetes prevention in the IDDM rat: Vitamin D and other compounds

16.55 – 17.10 Discussion

17.10 – 17.45 L Overbergh (KUL, Leuven)
Administrative Issues

19.00 Dinner in town

Tuesday, 23 Nov 2010

WP 1 – Re-educating antigen-presenting cells – WP leader B Roep

09.00 – 09.05 Bart Roep – Overview
09.05 – 09.20 T Nicolic (LUMC, Leiden)
Title: Generation of GMP grade DCs and future perspectives
09.20 – 09.35 F Kleijwegt (LUMC, Leiden)
Title: Mechanism of action of human Tregs generated by tolerogenic DCs
09.35 – 09.50 G Bomfim Ferreira (KUL, Leuven)
Title: Proteomic analysis of Vitamin D and Dexamethasone – modified DCs.
09.50 – 10.05 M-B Zocca (DanDrit, Denmark)
Title : SOPs and regulatory issues for clinical translation of DC therapy

10.05 – 10.20 Discussion

WP2 – Restoring the T-cell balance – WP leader M Peakman

10.20 – 10.25 M Peakman (KCL, London) – Overview
10.25 – 10.45 CM Dayan (CU, Cardiff)
Title: Progress on optimizing the tolerogenic potential of the skin for peptide immunotherapy
10.45 – 10.50 P Bingley (UB, Bristol)
Title: Establishing a clinical network for T1D mechanistic and intervention trials
10.50 – 11.00 M Peakman & V Gibson (KCL, London)
Title: Establishing a platform for multi-peptide immunotherapy
11.00 – 11.05 M Peakman (KCL, London)
Title: Phase Ib study of mono-peptide immunotherapy

11.05 – 11.20 Discussion

11.20 – 11.30 Coffee Break

WP3 – TCR-directed immunotherapy – WP leader C. Mathieu

11.30 – 11.35 C Mathieu (KUL, Leuven) – Overview
11.35 – 11.50 R Ashfield (IMC, Abingdon)
Title: Engineering T cell Receptors specific for beta-cell antigens
11.50 – 12.05 C Gysemans (KUL, Leuven)
Title: sTCR specific for beta-cell antigens in treatment of diabetes
12.05 – 12.15 S Megit (IMC, Abingdon)
Title: TCRs for human beta-cell antigens and future perspectives
12.15 – 12.35 J Demengeot (FCG, Lisboa)
Title: In vivo and in vitro suppression assays

12.35 – 12.50 Discussion

12.50 – 13.45 Lunch

13.45 – 14.30 Steering committee

WP 4 – Mucosal intervention for tolerance restoration – WP leader F Dotta

14.30 – 14.35 F Dotta (UNISI, Siena) – Overview
14.35 – 14.50 P Rottiers (AGX, Zwijnaarde/Ghent)
Title: Actobiotics™ in new onset T1D: development of prototypes of L. lactis strains expressing single and multiple beta-cell-specific antigen(s)
14.50 – 15.05 H Korf (KUL, Leuven)
Title: Use of recombinant ActoBiotics in preclinical mouse models
15.05 – 15.20 F Dotta (UNISI, Siena)
Title: L. rhamnosus GG and human iTreg in vitro induction

15.20 – 15.35 Discussion

15.35 – 15.55 Coffee Break

WP6 – Pharmacogenetics: towards individualised therapies – WP leader K Badenhoop

15.55 – 16.00 K Badenhoop (GUF, Frankfurt) – Overview
16.00 – 16.15 K Badenhoop (GUF, Frankfurt)
Title: Vitamin D genetics and peripheral immunity: Pilot study ViDDA1
16.15 – 16.30 E Ramos-Lopez (GUF, Frankfurt)
Title: Vitamin D pathway genes and vitamin D metabolites in T1D
16.30 – 16.45 Todd (UCAM, Cambridge)
Title: Vitamin D and TCR signaling: ongoing studies

16.45– 17.00 Discussion

WP8 – CP management and administration

17.00– 17.30 General Assembly

19.00 Dinner in town

Wednesday, 24 Nov 2010

Training Session – Part 2 – Location: Leibnizhaus Hannover – Room …

09.00 – 09.45 J Todd (UCAM, Cambridge)
Title: Genes and biomarkers in autoimmune diabetes
09.45 – 10.05 T Arndt (MHH, Hannover)
Title: Genetics of the IDDM (LEW.1AR1-iddm) rat model of human type 1 diabetes
10.05 – 10.35 H Korf (KUL, Leuven)
Title: Immune mouse models for type 1 diabetes

10.35 – 11.00 Coffee Break

11.00 – 11.45 S Lenzen (MHH, Hannover)
Title: Rat models of human type 1 diabetes

11.45 – 12.15 Discussion and closing remarks

End of Meeting

Scientific launch meeting of NAIMIT

Posted on | October 21, 2009 | No Comments

universiteitshallen

universiteitshallen


Universiteitshallen, Naamsestraat 22, B-3000 Leuven, Belgium

2 november 2009

Press release… read more

Naimit Partners


PROGRAM

9.00 – 17.00 Poster exposition of the participating research groups

9.00 – 9.10  Welcome by Prof. Dr. M. Waer, Rector Magnificus of the K.U.Leuven

9.10 – 9.40  NAIMIT project presentation (overview of the scientific goals) – Coordinator C. Mathieu

9.40 – 10.15  WP1 – Re-educating antigen-presenting cells – Chair B. Roep

  • B. Roep (LUMC, Leiden) 20’ – “Antigen-specific therapy with tolerogenic dendritic cells”
  • A. Wakatsuki-Pedersen (DanDrit, Copenhagen) 15’ – “Clinical application of dendritic cells”

10.15 – 11.15  WP2 – Restoring the T-cell balance – Chair M. Peakman

  • M. Peakman (KCL, London) 20 ’ – “Studies on T cells in Type 1 diabetes lead to new therapeutic options”
  • C. Dayan (UNIVBRIS, Bristol) 20’ – “Optimizing Peptide Immunotherapy in Type 1 diabetes”
  • P. Bingley (UNIVBRIS, Bristol) 20’ – “Assessing Type 1 diabetes risk: potential strategies and implications”

11.15 – 11.45   coffee break

11.45 – 12.40  WP3 – TCR-directed immunotherapy – Chair C. Mathieu

  • C. Mathieu (KULeuven, Leuven) 20’ – “Vitamin D and Type 1 diabetes”
  • J. Demengeot 20’ (FCG-IGC, Lisboa) – “Promoting regulatory T-cell differentiation and function: precursors,       location and environmental factors”
  • R. Ashfield (IMC, Oxford) 15’ – “Targeting beta-cell epitopes with high affinity T-cell receptors”

12.40 – 14.00   lunch

14.00 – 14.35  WP4 – Mucosal intervention for tolerance restoration – Chair F. Dotta

  • F. Dotta (UNISI, Siena) 20’ – “Probiotics, gut immune system and islet autoimmunity”
  • P. Rottiers (AGX, Ghent) 15’ – “ActoBiotics™: a novel tool for drug delivery”

14.35 – 15.35  WP5 – Beta-cell protection and restoration: dialogue with the immune system – Chair D. Eizirik

  • D. Eizirik (ULB, Brussels) 20’ – “Gene networks regulating beta-cell apoptosis and proinflammatory signals”
  • P. Marchetti (UPI, Pisa) 20’ – “Human islet isolation for Type 1 diabetes research”
  • S. Lenzen (MHH, Hannover) 20’ – “Analysis of protection strategies in type 1 diabetes animal models”

15.35 – 16.00   coffee break

16.00 – 16.40   WP6 – Pharmacogenetics: towards individualised therapies – Chair K. Badenhoop

  • K. Badenhoop (GUF, Frankfurt am Main) 20’ – “Vitamin D pathway genes and experimental Type 1 diabetes”
  • J. Todd (CIMR, Cambridge) 20’ – “Genes and phenotypes in Type 1 diabetes”

16.40 – 17.00   General discussion & closure


Launch of NAIMIT project to cure diabetes (Type1)

Posted on | October 21, 2009 | No Comments

Natural immunomodulators as novel immunotherapies for type 1 diabetes

Type 1 diabetes melllitus (T1DM) is an autoimmune disease characterised by immune-mediated destruction of insulin-producing beta-cells in the pancreas. The incidence of T1DM in childhood is increasing at about 3% per year, equivalent to a doubling time of 20-25 years. T1DM is the most common metabolic disease in the young. In addition, 5-10% of patients originally diagnosed as T2DM have a less severe and more slowly progressing form of T1DM, usually referred to as “Latent Autoimmune Diabetes of Adults” (LADA).

About two million people in Europe (around 0.5% of the population) and several million people world-wide suffer from this disease.

Of concern are the reports of a steady increase of T1DM over the last decades in virtually all European countries and a particular escalation in the 1-5-year age group. Since it carries a significant chronic disease burden, T1DM has thus become a major public health concern worldwide, emphasizing the urgent need for safe and effective intervention and prevention strategies. At the same time that this gloomy picture has emerged, a series of key basic and clinical scientific advances have promoted the concept that reversing autoimmunity in type 1 diabetic (T1DM) patients has become a reachable challenge through growing insight in the pathogenesis of the disease and the availability of novel tools allowing interference with the disease process.

We propose an original concept, in which natural immune modulators will be introduced in interventional approaches that will modify the immune system through an antigen-specific route to achieve beta-cell protection.

Only by intervening in an antigen specific way can one guarantee beneficial immunomodulation with minimal unwanted immune perturbation in the quest to reverse autoimmunity. In NAIMIT we propose to come to tailored interventions with minimal immune system interference in new onset T1DM, leading to beta-cell protection and restoration, based on a solid understanding of the disease pathogenesis. This will enable experimental findings to be adopted for future clinical application. To achieve these ambitious goals, we have established a multidisciplinary consortium of leading European diabetologists and immunologists from 11 academic research institutions, in co-operation with 3 SMEs developing novel technologies allowing translation of basic research results towards clinical applications.

The NAIMIT approach is integrated, moving from a specific hypothesis on the pathogenesis of T1DM, supported by present state-of-the-art research, to interventions targeting the different players in the destruction of the beta-cell. The concept of this proposal is to target the immune components using natural immunomodulators and novel technologies for their delivery, thereby modulating the immune system in a targeted fashion and to a minimal degree only. This will allow arrest of autoimmunity while avoiding undesirable side effects. Two key players of the immune system in beta-cell destruction will be targeted: the DC (WP1: Re-educating antigen-presenting cells) and the T lymphocyte (WP2: Restoring the T-cell balance). In both cell types, interventions using steroid hormones (vitamin D and glucocorticoids) will be used in order to induce tolerogenic cell types. Moreover, novel interventions using soluble TCR to target immune cells and beta-cells in an antigen-specific way (WP3: TCR-mediated immunotherapy). Novel mucosal interventions using recombinant L. lactis (ActoBiotics™) as a carrier for specific peptides in combination with cytokines (WP4: Mucosal intervention for tolerance restoration) will be studied for their potential to interfere with the immune system.

An important asset of NAIMIT is that in addition to consideration of immune cells, the role of the beta-cell in its own destruction and the pathways involved in its demise will be studied.

Particular attention will be paid to understanding the communication pathways between beta-cells and the immune system, opening new ways to arrest progression of autoimmunity and preserve beta-cell mass (WP5: Beta-cell protection and restoration). Finally, we will move towards individual tailoring of therapy. Using a pharmacogenetic approach, applicable to the designed interventions, we will evaluate the potential for individualised intervention strategies (WP6: Pharmacogenetics). The results to be obtained will not only open the door to novel intervention therapies with minimal modulation of the immune system in newly diagnosed T1DM individuals, but will also improve our understanding of the disease process.

    About

    NAIMIT is an Collaborative Project funded by the European Union's 7th Framework Programme (FP7) and coordinated by the Laboratory of Experimental Medicine and Endocrinology at the Catholic University of Leuven (KUL).

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