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Efficacy and safety of low-dose IL-2 (ld-IL-2) as a Treg enhancer for anti-neuroinflammatory therapy in newly diagnosed Amyotrophic Lateral Sclerosis (ALS) patients

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.

Field of science

  • /medical and health sciences/basic medicine/neurology/amyotrophic lateral sclerosis

Call for proposal

H2020-PHC-2014-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

CENTRE HOSPITALIER UNIVERSITAIRE
Address
Place Du Pr Robert Debre
30900 Nimes
France
Activity type
Research Organisations
EU contribution
€ 1 448 890,33

Participants (11)

INSERM TRANSFERT SA
France
EU contribution
€ 421 000
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ICON CLINICAL RESEARCH LIMITED
Ireland
EU contribution
€ 659 105
Address
South County Business Park Leopardstown
18 Dublin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ASSOCIATION GENETHON
France
EU contribution
€ 373 622,50
Address
Rue De L Internationale 1 Bis
91002 Evry
Activity type
Research Organisations
HUMANITAS MIRASOLE SPA
Italy
EU contribution
€ 450 000
Address
Via Manzoni 56
20100 Rozzano (Mi)
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
GOETEBORGS UNIVERSITET
Sweden
EU contribution
€ 140 500
Address
Vasaparken
405 30 Goeteborg
Activity type
Higher or Secondary Education Establishments
THE UNIVERSITY OF SUSSEX
United Kingdom
EU contribution
€ 856 330,09
Address
Sussex House Falmer
BN1 9RH Brighton
Activity type
Higher or Secondary Education Establishments
THE UNIVERSITY OF SHEFFIELD
United Kingdom
EU contribution
€ 504 408,13
Address
Firth Court Western Bank
S10 2TN Sheffield
Activity type
Higher or Secondary Education Establishments
KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 490 790
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
QUEEN MARY UNIVERSITY OF LONDON
United Kingdom
EU contribution
€ 159 138,75
Address
327 Mile End Road
E1 4NS London
Activity type
Higher or Secondary Education Establishments
MOTOR NEURONE DISEASE ASSOCIATION
United Kingdom
EU contribution
€ 0
Address
10 15 Notre Dame Mews
NN1 2BG Northampton
Activity type
Other
WGK CONSULTANCY LTD
United Kingdom
EU contribution
€ 476 650,20
Address
29 Sish Lane
SG1 3LS Stevenage
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)