PMSMatTrain — Novel Biomaterial-based Device for the Treatment of Progressive MS- - An Integrated Pan- European Approach

Results in brief

Novel Biomaterial-based Device for the Treatment of Progressive MS- - An Integrated Pan- European Approach

Multiple Sclerosis is an inflammatory demyelinating disorder of the brain caused by an immune system attack on myelin and/or the cells that produce myelin (oligodendrocytes) and support neurons. This leads to a widespread loss of neuronal function and deficits in executive and cognitive functions, which result in a major loss of quality of life and independence for the 2.3 million people with MS worldwide. Moreover, MS pathology is a self-perpetuating deleterious cycle of neuroinflammation and neurodegeneration that leads to neuronal loss. Over time, individuals commonly enter a protracted, chronic degenerative phase of the disease, known as progressive multiple sclerosis (PMS). Two anti-inflammatory treatments, ocreluzimab and siponimod, have recently been approved for the treatment of PMS, but less than half of individuals with PMS are suitable for these therapies. Moreover, systemic medical treatment such as these is limited by the inability of drugs to cross the blood-brain barrier. The particular issues being addressed by this project are an incomplete understanding of the molecular underpinnings of disease course and pathology and the sub-optimal management of the disease course. An improved understanding of the biological changes occurring in the immune and central nervous systems should help to identify novel targets for MS therapy, improve drug delivery platforms and increase the proportion of individuals that receive and are responsive to disease-modifying therapies. This is important for society as a whole, as successful MS therapies enable those living with MS to be employed for longer, placing less of a burden on healthcare systems the other family members. The overall objectives of the research carried out by members of the PMSMatTrain consortium were to do the following: 1) develop improved lab-based and pre-clinical models of MS pathology; 2) use these models to test candidate drugs that inhibit inflammation and promote the repair of damaged nerves; 3) design a novel, minimally-invasive device that targets in particular, disease in the outer layers of the brain (the cortex); 4) facilitate slow, long-term release of drugs from the device, using ‘tuneable’ bio-based hydrogels.

Data: CORDIS, © European Union

Project objective

PMSMatTrain is focusing on gaining a comprehensive understanding of the progressive (late degenerative phase) of multiple sclerosis (PMS) from basics to translation, fully supported by 8 beneficiaries (6 research institutions, 2 SMEs). Recruited ESRs will receive compulsory discipline-specific, generic and complementary transferable skills training. PMSMatTrain’s Joint Research Education and Training programme (JRTP) will provide early stage researchers with high quality research and transferable skills training in intellectual property, leadership skills, innovation, regulatory affairs, entrepreneurship, gender policy, and medical device evaluation, which will ensure that they are immediately employable in industry. The consortium will develop a multi-modal hyaluronan-based medical device designed to release small molecular weight anti-inflammatory molecules (APRIL and sPIF) followed by remyelination and neuroprotective drugs (ibudilast and miconazole). PMSMatTrain will for the first time utilise these functionalised multi-modal biomimetic hyaluronan scaffolds as a tool to investigate cross-talk between signals arising due to chronic neuroinflammation and those leading to demyelination and axonal loss, while identifying molecular mechanisms that facilitate remyelination and neuroprotection in PMS. This approach could yield the first cortex-proximal and directed biomaterials-based disease-modifying therapy for PMS. These scaffolds will be tested in state of the art MS patient induced stem cell-derived oligodendrocyte cultures and organotypic cultures to investigate MS pathophysiology. In vivo responses will be characterised using field-leading MRI and mass spectrophotometry protocols. PMSMatTrain will also generate a clinically-relevant in silico model of drug elusion and dispersal within the CNS. Our industry partners will develop the end-device by providing standardised manufacturing protocols for scaled-up production and commercialisation of the cGMP product.

Original text from CORDIS.

Participants

UNIVERSITY OF GALWAY · GalwayCoordinatorIreland
CONTIPRO AS · DOLNI DOBROUCCzechia
NEOS SURGERY SL · DONOSTIA SAN SEBASTIANSpain
SYDDANSK UNIVERSITET · Odense MDenmark
UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA · ChietiItaly
UNIVERSITAET MUENSTER · MuensterGermany
UNIVERSITE GRENOBLE ALPES · GrenobleFrance
UNIVERSITEIT ANTWERPEN · AntwerpenBelgium

PMSMatTrain · Novel Biomaterial-based Device for the Treatment of Progressive MS- - An Integrated Pan- European Approach

Results in brief

Novel Biomaterial-based Device for the Treatment of Progressive MS- - An Integrated Pan- European Approach

Project objective

Participants

Links