UEPHA-MS

United Europeans for the Development of Pharmacogenomics in Multiple Sclerosis

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 Obiettivo del progetto (Objective)

'Multiple sclerosis (MS) is a chronic inflammatory, disabling disease of the central nervous system. Recent studies suggest that over the last 50 years a disproportional increase in incidence of MS in women has taken place. The lifetime costs of MS exceed 1.5 million € per case in the UK, and are likely to be similar in other European countries. There is no definitive cure for MS. Immunomodulatory therapies, such as interferon-β (IFN-β) and glatiramer acetate (GA), are only partially effective. Hence, there is a pressing need both for novel therapeutic targets and for approaches toward increasing the effectiveness of these existing treatments. The focus of the proposed “United Europeans for the development of PHArmacogenomics in MS” (‘UEPHA-MS’) network will be to promote and improve training opportunities in the novel areas of pharmacogenomics, biomarker research and systems biology applied to MS. The main scientific goals of this network are both to improve our knowledge of the mechanisms determining response outcome of existing immunomodulatory therapies and to identify novel therapeutic opportunities. UEPHA-MS is composed of ten internationally recognised research teams from 6 countries with an assortment of expertise in complementary disciplines. UEPHA-MS partners are among Europe’s most pro-active groups in pioneering the novel, supra-disciplinary area of integrated genomics / bioinformatics / systems biology research. The UEPHA-MS network will provide a coherent and internationally competitive platform for training of young scientists based on a series of state-of-the-art lab-based and network-wide activities. UEPHA-MS will boost employment perspectives of young researchers in Europe’s knowledge-based economy by shaping a new generation of scientists with greatly enhanced multidisciplinary aptitudes. This network will be crucial in priming young scientists for Europe’s collective effort toward improved provision of health care based on “personalized medicine”.'

Introduzione (Teaser)

Multiple sclerosis (MS) is a chronic inflammatory disorder where the body mounts an abnormal immune response against the central nervous system. Predicting disease severity and clinical response using biomarkers would significantly improve disease management.

Descrizione progetto (Article)

In MS, the immune system targets the myelin sheath around nerve cells. A damaged myelin sheath translates into distorted nerve impulses traveling to and from the brain and spinal cord, causing a variety of symptoms.

MS has a variable clinical picture and patients show a diverse response to standard therapeutic treatments. The existence of genetic determinants that shape patients' response to therapy is gaining momentum in the field of MS research. Based on this, scientists on the EU-funded 'United Europeans for the development of pharmacogenomics in multiple sclerosis' (UEPHA-MS) project proposed a pharmacogenomics analysis in patients with MS in response to standard therapies (interferon (IFN) beta, glatiramer acetate (GA) and natalizumab).

Toll-like receptor 4 and IFN signalling pathways were key factors in IFN-beta therapy response while natural killer cells were a requisite for other clinical responses. Researchers validated the genetic component by selecting over 380 single nucleotide polymorphisms associated with therapy outcome as well as susceptibility to disease.

Since MS is a heterogeneous disease, predictive and diagnostic biomarkers are essential for patient stratification. To this end, the UEPHA-MS project performed omics analysis in patients and identified drug response biomarkers as well as disease severity biomarkers. The latter substantiated a role for T and B lymphocyte activation pathways in MS severity.

Considerable part of the UEPHA-MS project entailed the training of young investigators in cutting-edge technologies for biomarker research. The activities included laboratory training, courses and workshops, as well as three summer schools.Taken together, the UEPHA-MS findings considerably enhanced our capacity to perform prognosis, diagnosis and predict the outcome of therapy for MS patients. The generated information will undoubtedly make drug management and monitoring in MS much more precise and effective.