Objective Amyotrophic Lateral Sclerosis (ALS) is a fatal degenerative disorder of the brain and spinal cord affecting some 40,000 individuals in Europe, causing 11,000 deaths each year. Our pioneering work on riluzole showed that it is possible to modify ALS progression but all subsequent trials of potential neuroprotective agents have failed. Thus, drug development in ALS, including trial design, patient selection, and outcome measures must be re-engineered to break the current impasse. Nerve cell death in ALS is associated with inflammation, which contributes to cell damage, and is a logical target for therapy. Although therapeutic attempts to modify this have failed so far, the discovery of regulatory T cells (Tregs) as key players in controlling inflammatory processes opens new possibilities since defective Treg function is important in ALS. In fact, Treg numbers and function predict rates of disease progression and survival. Low-dose interleukin-2 (ld IL-2) safely and specifically increases and activates Tregs in conditions such as type 1 diabetes, HBc-vasculitis and chronic graft-versus-host disease, so ld IL-2 has the potential to significantly improve survival and deliver a therapeutic breakthrough in ALS. We also integrate biomarkers for nerve cell damage into the trial design to provide proof of concept/mechanism. “Modifying Immune Response and OutComes in ALS” (MIROCALS) will test the hypothesis that ld IL-2-induced increases in Tregs result in decreased rates of nerve cell damage and that this effect can be detected early in the course of the disease using a range of blood and cerebrospinal fluid biomarkers. Our ambition is to develop a new therapy for ALS and through this novel trial design break the impasse in drug development of other disease-modifying agents in ALS. The impact will be to enhance quality of life and care for people with ALS, and provide a robust model for Industry to encourage investment in ALS and other neurodegenerative diseases. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineemergency medicinegraft versus host diseasemedical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Keywords Amyotrophic Lateral Sclerosis Neurodegenerative Disease RCT Phase -II Proof of Concept Proof of Mechanism low-dose Interleukin-2 regulatory T cells anti-inflammatory therapy Programme(s) H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being Main Programme H2020-EU.3.1.3. - Treating and managing disease Topic(s) PHC-13-2014 - New therapies for chronic non-communicable diseases Call for proposal H2020-PHC-2014-2015 See other projects for this call Sub call H2020-PHC-2014-two-stage Funding Scheme RIA - Research and Innovation action Coordinator CENTRE HOSPITALIER UNIVERSITAIRE Net EU contribution € 1 505 681,28 Address PLACE DU PR ROBERT DEBRE 30900 Nimes France See on map Region Occitanie Languedoc-Roussillon Gard Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 505 681,28 Participants (14) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSERM TRANSFERT SA France Net EU contribution € 421 000,00 Address 10 RUE D'ORADOUR-SUR-GLANE - PARISANTE CAMPUS 75015 PARIS See on map Region Ile-de-France Ile-de-France Paris Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 421 000,00 ICON CLINICAL RESEARCH LIMITED Ireland Net EU contribution € 13 996,25 Address SOUTH COUNTY BUSINESS PARK LEOPARDSTOWN 18 Dublin See on map Region Ireland Eastern and Midland Dublin Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 659 105,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. ICON CLINICAL RESEARCH (U.K.) LIMITED United Kingdom Net EU contribution € 217 555,00 Address 6 STONEYCROFT RISE CHANDLERS FORD SO533 LD Hampshire See on map Region South East (England) Hampshire and Isle of Wight South Hampshire Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 217 555,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. ICON CLINICAL RESEARCH GMBH Germany Net EU contribution € 18 357,50 Address HEINRICHT HERTZ STRASSE 26 63225 Langen See on map Region Hessen Darmstadt Offenbach, Landkreis Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 18 357,50 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. ICON CLINICAL RESEARCH France Net EU contribution € 409 196,25 Address 55, rue des Champs Pierreux. Immeuble Le Capitole 92000 Nanterre See on map Region Ile-de-France Ile-de-France Hauts-de-Seine Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 409 196,25 ASSOCIATION GENETHON France Net EU contribution € 373 622,50 Address RUE DE L INTERNATIONALE 1 BIS 91002 Evry See on map Region Ile-de-France Ile-de-France Essonne Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 373 622,50 HUMANITAS MIRASOLE SPA Italy Net EU contribution € 450 000,00 Address VIA MANZONI 56 20100 Rozzano (Mi) See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 450 000,00 GOETEBORGS UNIVERSITET Sweden Net EU contribution € 140 500,00 Address VASAPARKEN 405 30 Goeteborg See on map Region Södra Sverige Västsverige Västra Götalands län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 140 500,00 THE UNIVERSITY OF SUSSEX United Kingdom Net EU contribution € 856 330,09 Address SUSSEX HOUSE FALMER BN1 9RH Brighton See on map Region South East (England) Surrey, East and West Sussex Brighton and Hove Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 335 025,79 THE UNIVERSITY OF SHEFFIELD United Kingdom Net EU contribution € 504 408,13 Address FIRTH COURT WESTERN BANK S10 2TN Sheffield See on map Region Yorkshire and the Humber South Yorkshire Sheffield Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 504 408,13 KING'S COLLEGE LONDON United Kingdom Net EU contribution € 490 790,00 Address STRAND WC2R 2LS London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 490 790,00 QUEEN MARY UNIVERSITY OF LONDON United Kingdom Net EU contribution € 159 138,75 Address 327 MILE END ROAD E1 4NS London See on map Region London Inner London — East Tower Hamlets Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 159 138,75 MOTOR NEURONE DISEASE ASSOCIATION United Kingdom Net EU contribution € 0,00 Address 10 15 NOTRE DAME MEWS NN1 2BG Northampton See on map Region East Midlands (England) Leicestershire, Rutland and Northamptonshire West Northamptonshire Activity type Other Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 51 611,25 WGK CONSULTANCY LTD United Kingdom Net EU contribution € 419 859,25 Address 29 SISH LANE SG1 3LS Stevenage See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region East of England Bedfordshire and Hertfordshire Hertfordshire Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 419 859,25