Currently, there are six new drugs that are being assessed by clinical scientists and a few of these drugs have moved into or completed stage 2 level and stage 3 level specialized medical trials. Three of the drugs are dental drugs and they include Lanquinimod, Teriflumomide and Di-methyl fumarate. The other three are monoclonal antibodies (mAb) particularly Alemtuzumab, Daclizumab and Rituximab (Borrero et al, 2012). Many of these drugs target the immune system in different ways however, many of them still present with some part effects as well which are discussed below.
Starting with Lanquinimod, it can be an immunomodulator that happens to be being trialled in patients with RRMS and SPMS. It includes a very small recommended dosage of 0. 6 mg daily and it displays anti-inflammatory properties. These properties are believed to support the downregulation of MHC class II transcription factors, stimulation of neurotrophic factors, activation and up-regulation of the IL-4 pathway in Disc4+ T cell for anti-inflammatory results. It also helps bring about apoptosis in Cytotoxic T-cells (Disc8+) and B-cells and also suppresses metabolism in CD14+ and natural killer cells (Th¶ne et al. , 2016). It is currently undergoing Stage III tests and has led to 23% decrease in the speed of relapse of MS while there's been a 37% reduction in contrast improving lesions in volunteers (Borrero et al, 2012). Its side-effect is only the upregulation of Liver Function Exams (LFTs)
The second oral medicine that is considering phase III professional medical trials is Teriflunomide which is being trialled for patients with RRMS and SPMS. Doses which range from 7 to 14 mgs daily are advised to be implemented orally in patients. Its function of action depends upon sequestering the production of DNA pyrimidine bases by acting as an inhibitor for the enzyme dihydroorotate dehydrogenase, which is essential in de novo pyrimidine synthesis in T and B skin cells that are rapidly dividing. This reduces any inflammation that would've been induced by those cells and thus immune system suppression is achieved. Relating to Borrero et al, it includes a success rate of 61% in lowering contrast boosting lesions, an interest rate of 30% in lowering Annualized relapse rates (ARRs) and disability progression was detected to be reduced to 23-30%. Terfilunomides's aspect results include Nasopharyngitis; which is the inflammation of the nasopharyngeal duct, diarrhoea, again pain, fatigue, baldness, influenza, URINARY SYSTEM Illness (UTI), nausea and enhanced LFTs (Borrero et al, 2012).
The third dental drug is Di-methyl fumarate (DMF) or BG-12. It is also considering type III specialized medical studies for patients with RRMS. Its suggested dose is 120-24 mg three times each day. It has shown a decrease of 69% in contrast improving lesions in its stage II trial and its phase III trials have up to now showed 53% reduction in ARR, 38% decrease in disability progression and in 24 months, by 49% (Borrero et al, 2012). Di-methyl fumarate's function of action continues to be being debated but it is believed so it can control oxidative pathways which may in turn influence other signalling pathways that are accountable for inducing tissue damage. Tests by Moharregh -Khiabani et al in '09 2009 demonstrated that DMF acquired an inhibitory effect on the nuclear factor NFОєB dependant, TNF О± induced gene transcription in endothelial skin cells. It is also presumed that DMF can energize skin cells to secrete cytokines such as IL-10, IL-4 and IL_5 which have anti-inflammatory properties thus allowing a more Th2 targeted response when compared to a Th1 one (Wierinckx et al. , 2005). Additionally, DMF is thought to have a neuroprotective therapeutic impact as well. This occurs as it triggers an upregulation in the levels of the cleansing enzyme; NADPH but like other emerging drugs, it includes side results. These side effects include diarrhoea, cramps, elevated LFT, nausea and can cause flushing and in very rare cases, Progressive multifocal leukoencephalopathy (PML) (MS Modern culture 2016).
Other novel therapies include the use of monoclonal antibodies (mAb) for the treatment of MS. As of now, there are three that are undergoing period II and III studies respectively. Alemtuzumab is one such mAb that is within its stage III medical trial for patients with RRMS and SPMS. Its recommended dose is Intravenous infusion of 12- 24 mg daily for a course of 5 days every month if it's a 1 year course which is increased to 24mg on the 12th month. Its mode of action is causing the devastation of circulating immune cells by binding to Compact disk52 on mature leukocytes which results in the lysis of Compact disk4+ and Compact disk8+ T cells, B cells, eosinophils, NK skin cells, monocytes and macrophages as well (Hart and Bainbridge 2016). In phase III studies, it has so far shown up to 75% reduction in sustained accumulation disability and up to 74% decrease in relapse rate but has been associated with potentially increasing the chance of autoimmunity which included thyroiditis, idiopathic thrombocytopenic purpura, autoimmune thyroid-related problems, Goodpasture's symptoms and also, can cause flushing and headaches (Borrero et al, 2012). By yet, it is not approved by the FDA as it is still undergoing tests but it can be used as a medication for treating a form of blood cancer tumor called B-cell chronic lymphocytic leukaemia (B-CLL) (FDA 2016).
References
https://www. researchgate. net/profile/Anne_Wierinckx/publication/7750124_Detoxication_enzyme_inducers_modify_cytokine_production_in_rat_mixed_glial_cells/links/0c960534be656953a2000000/Detoxication-enzyme-inducers-modify-cytokine-production-in-rat-mixed-glial-cells. pdf
https://www. ncbi. nlm. nih. gov/pmc/articles/PMC2724664/
http://journals. sagepub. com/doi/pdf/10. 1177/1756285612450936
https://www. fda. gov/Drugs/DrugSafety/ucm082681. htm
http://www. ajmc. com/journals/supplement/2016/cost-effectiveness-multiple-sclerosis/cost-effectiveness-multiple-sclerosis-current-emerging-treatment/P-3
https://www. mssociety. org. uk/what-is-ms/treatments-and-therapies/licensed-disease-modifying-drugs/Tecfidera
