Role of ADA SNPs in Subjects With Relapsing Multiple Sclerosis (RMS)

Summary

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), which is highly heterogeneous in terms of clinical symptoms, MS subtypes and treatment response. In each patient with MS, inflammatory, neurodegenerative and reparative processes are intermingled in different proportions, making the disease course unpredictable and the treatment approach challenging. Although MS etiology is still unclear, many studies have demonstrated that T and B cells are crucial cellular determinants of MS pathophysiological processes. Auto-reactive T lymphocytes have been also implicated in excitotoxic synaptopathy, an early hallmark of MS recently emerged to link inflammation and neurodegeneration in a complex and inter-regulated circuit. In addition, several reports published in the last few years show the presence of a link between metabolism and immune responses. Indeed, it is now clear that cell metabolism is able to control T cell survival, growth, activation and differentiation. It has been reported that distinct metabolic pathways are able to support specific T cell activities suggesting that the delicate balance among glycolysis, fatty acid oxidation (FAO) and mitochondrial respiration drives specific effector (Tconv) and regulatory T cell (Treg) differentiation and functions. The individual response to treatment varies widely and their use may be burdened by side effects and major adverse events. An explanation of the clinical and pharmacological individual variability can be sought in the pathological heterogeneity and in different genetic, immunological and metabolomics profiles. With this perspective, the lack of a single predictive or diagnostic test remains a great obstacle in the management of MS at most stages and in the choice of the therapy. Consequently, the availability of biomarkers that reliably capture the different aspects of the disease could be extremely useful.

Eligibility

Inclusion Criteria:

1. Male or female subjects ≥ 18 years old
2. Subjects candidate to be treated with Cladribine (2-CdA) according to clinical practice and meeting the SmPc requirements:

   * Body weight ≥ 40 Kg
   * Highly active RMS as defined by: One relapse in the previous year and at least 1 T1 Gd+ lesion or 9 or more T2 lesions, while on therapy with other disease modifying drugs (DMDs); two or more relapses in the previous year, whether on DMD treatment or not;
3. Normal lymphocyte count (absolute values 1.0-3.0×109/l) according to Cladribine local labelling;
4. EDSS score ≤5.0.

Exclusion Criteria:

1. Previous exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab;
2. Positive hepatitis C or hepatitis B surface antigen test and/or hepatitis B core antibody test for IgG and/or IgM;
3. Current or previous history of immune deficiency disorders including a positive human immunodeficiency virus (HIV) result;
4. Currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids;
5. History of tuberculosis, presence of active tuberculosis, or latent tuberculosis;
6. Evidence or suspect of PML in MRI;
7. Active malignancy or history of malignancy.
8. Pregnant or lactating women
9. Currently receiving interferon

Conditions2

Browse More Trials