Last Saturday we attended the MS Forum VI in the Mandarin Oriental of Brickell Key, Florida, where we discussed with prestigious academicians and colleagues the latest developments in the treatment of myriad clinical presentation of Multiple Sclerosis. Amongst the topics that were exposed about, we selected to discuss three with you:
- Anti-CD20 Monoclonal antibodies
- Oral therapies for relapsing MS
- Autologous Mesenchymal Stem Cells.
A – Anti-CD20 Monoclonal antibodies
These antibodies have been used to deplete the B cells proliferative disorders like leukemia and Hodgkin’s Disease for a few years already. CD-20 is a transmembrane calcium channel implicated in the B cell activation and differentiation; anti-CD20 target the B cells in an intermediate stage of their evolution, safeguarding the needed long-term immunological memory and the production of cells after depletion. The drug Rituximab was the first one approved for auto-immune disorders but it soon generated side effects due to the patients’ formation of anti-chimeric antibodies. At present there are many humanized versions of it that are being tested in clinical trials. In 2004 the Food and Drug Administration (FDA) approved the use of Natalizumab for the treatment of Multiple Sclerosis, heralding the era of MABs for its treatment. Alemtuzumab and ocrelizumab followed in the pipeline and were approved; at present ublituximab and ofatumumab are in the Phase III of their clinical trials. When we discussed a young patient with new onset of MS, most of us opted for Natalizumab as the drug of choice because it shows greater efficacy to thwart the symptoms early on with the caveat that it also elicits a quick rebound phenomenon.
B – Oral therapies for relapsing MS
Even though Interferon B or Copaxone are often the first drugs of choice, many patients prefer the oral therapies like Fingolimod, Teriflunomide and Dimethyl Fumarate. In 2010 Fingolimod became the first FDA-approve oral therapy. In the Confine and Define clinical trials, Dimethyl Fumarate has been shown to reduce the relapse rates, the number of lesions in the MRI scans and the physical disabilities; its efficacy might be due to its anti-inflammatory properties to decrease oxidation; it modulates the sphingosine-1-receptor and decreased the lymphocyte migration to the CNS. Compared to Interferon beta-1a has been shown to reduce 52% the yearly relapses in one study; after one year, 13% of patients did not have any relapses. In the Temso trial, Terifluamide reduced the yearly rates of relapses, the MRI lesions and the physical disability limitations; the drug blocks the pyrimidine synthesis, which decreases the inflammatory process, including the production of white cells in the CNS and the protection of the myelin sheaths of the nerves.
C – Autologous Mesenchymal Stem Cells
Stem Cell transplant is an emerging, promising new therapy for MS, which has been discussed in the professional and public forums for the past few years. Patient that come to the office invariably ask us: “what do you think about Stem Cells, doctor?’ However there has been a dearth of reliable clinical trials with proper peer supervision until the early results of a Swedish study where presented in the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) that was held in Stockholm last September. The researchers discussed the positive data from the Nordic study of the Autologous Hematopoietic Stem Cell Transplant (AHSCT) that implies the harvesting of bone marrow from the patient and the use of chemotherapy to wipe out the rest. The patient’s own stem cells are then re-introduced in another surgical procedure. The results of a phase III randomized clinical trial showed that the NEDA (no evidence of disease) in the cohort treated with the AHSCT was 78.% compared to only 2.97% of patients treated with the conventional methods; the risks are the expected ones for the surgical interventions.
What do you think? Please tell us.
Don’t leave me alone.