Friends of Multiple Sclerosis articles

New Prospect of Multiple Sclerosis Treatment
    Multiple sclerosis is an autoimmune disease , the first clinical symptoms occur in young people. Clinically, according to the progression of multiple sclerosis can be divided into four categories , relapse - remitting : Relapsing-Remitting MS (RRMS), secondary - progressive : Secondary Progressive MS (SPMS), starting - progressive : Primary progressive MS (PPMS) and progressive - relapsing forms : Progressive Relapsing MS (PRMS). The progress of their disease can be briefly divided into two stages, relapse - remitting Relapsing-Remitting phase (RR phase) is mainly caused by the immune inflammatory response , and in the progressive stage progressive phase contains nerve degeneration. Immune induced inflammation is more specific mechanisms , and reaction mechanisms of degradation are still many uncertainties , so the current treatments have focused on the immune induced inflammation . FDA has approved a total of six kinds of drugs treating MS, can be divided into immunomodulatory agents Immunomodulator (Interferon-b 1a, Interferon-b 1b subcutaneously , Interferon-b 1a intramuscular injection , glatiramer acetate) immunosuppressants Immunosuppressant (mitoxantrone), as well as single polyclonal antibody (natalizumab).
 Immunomodulatory agents:
    Since 1993 Interferon - b 1b determined the efficacy of the MS , MS therapeutic drug development many of them move in this direction. Have been approved successively Interferon-b 1a ( subcutaneous and intramuscular two formulations ) and Glatiramer acetate (GA). GA is composed of four amino acids randomly formed polymer. Glatiramer acetate less common in Taiwan . Substantially Interferon - b therapeutic effect , can be reduced about 30% of the number of recurrences . However, its price is not Fei , takes about three a year , four hundred thousand . Interferon - b has the advantage of security.
 Immunosuppressive drugs:
    October 2000 was approved by the FDA for MS mitoxantrone treatment drugs . Mitoxantrone is an anticancer medicine, which has long been used to treat leukemia , prostate cancer, breast cancer , lymphoma and liver cancer. Mitoxantrone treatment of MS mechanism is in its broad immunosuppression , which inhibits T-cell and B-cell and macrophage proliferation , so that autologous antibodies to attack the central nervous system does not .Mitoxantrone in cancer month dose of 12mg / m 2, injection of 30 minutes. FDA approved for MS treatment usage per month 12mg / m 2, injection 30 minutes , this usage is based on the MIMS trial results. With Mitoxantrone pharmacokinetics of view , Mitoxantrone is a three compartment model, it will accumulate in the heart, liver , spleen and other organs, and slowly released, completely freed of three months or so. So every three months using is understandable . However, some studies have found that every three months using mitoxantrone, six months will have to be immunosuppressive effect, if the use of mitoxantrone every month just three months, so a more reasonable usage is that the first three months of the induction period induction phase with monthly injections 12mg/m2/month, and then in the maintenance phase maintenance phase every three months 12mg / m 2.Mitoxantrone restrict the use of the maximum cardiac toxicity, and the use of dose which , when the cumulative doses greater than 140mg / m 2 , the more prone to cardiac toxicity. Terms of use 12mg/m2 every three months to count , mitoxantrone only use up to three years , although the study found that there is still disabled immunosuppressive treatment within a year , an average duration of 30 years with MS perspective , mitoxantrone can use the term apparently too short.In addition to mitoxantrone, other immunosuppressants such as azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, tacrolimus has a short-term experiments confirmed the efficacy of the MS . However, these drugs must monitor its side effects, such as cyclophosphamide can cause hemorrhagic cystitis, methotrexate even at low doses will cause liver toxicity , mycophenolate mofetil, tacrolimus and azathioprine bone marrow suppression.
 Monoclonal antibodies :
    U.S. FDA in November 2004 approved natalizumab ( trade name TYSABRI) used to treat multiple sclerosis. This is a new type of medication that belongs to a synthetic monoclonal antibodies. Multiple sclerosis lesions mainly by activated white blood cells ( such as T- lymphocytes ) through the blood - brain barrier (blood-brain barrier, BBB), into the brain tissue caused by an inflammatory response. The process must be drilled BBB leukocytes by adhesion molecules on its surface mating with intimal cells binding to accept the job . Natalizumab on with leukocyte α 4 - integrin binding , and thus disrupt the α 4 - integrin and vascular cell adhesion molecule vascular walls -1 (vascular cell adhesion molecule -1, VCAM-1) interactions , leukocyte like this more difficult to drill into tissue caused by vascular endothelial inflammation . In addition, it can also affect the α 4 - integrin with the extracellular matrix and parenchymal cells, the role of other molecules , thereby inhibiting the inflammatory cells to attract more . Can be found in animal experiments can indeed reduce the use of natalizumab into the brain parenchyma cells, white blood cells and reduces the MRI detected lesions.In clinical trials , TYSABRI once every four weeks to implement intravenous injection relative to the control group decreased by 66% the number of episodes per year (0.25 vs. 0.74). Track of the year the treatment group compared to 76% of the attack , the control group was 53% ; NMR of new lesions in the treatment group also had significantly reduced. Also in an original in the use of Avonex ( one kind of beta interferon ) plus TYSABRI patients in the trial, also seen in relapses and MRI have a significant effect. For long-term use are in safety or efficacy have changed there is still no adequate information . Patients currently receiving treatment in <1% of patients have a strong allergic reaction.Alemtuzumab is a CD52 antibody . rituximab (Rituxan) for the CD20 α b antibody , daclizumab (Zenapax) compared with interleukin 2 receptor α -chain antibody .In summary , this new type of drug for multiple sclerosis This provides another intractable diseases the treatment of choice . Its long-term efficacy are inconclusive , must wait for more clinical experience accumulated only conclusion.
 Statins:
    Statins are HMG Co-A reductase antagonist , used to lowering blood pressure is well known . It is used in the treatment of MS is because in vitro findings , Statins can inhibit T-cell and B-cell activity , there are many possible mechanisms . Statins now been confirmed in the theoretical stage , to use in the treatment of MS remains well-designed experiments to confirm , particularly cholesterol in the general dose of whether the effect of this immunosuppressive , still worth progress discussed.
 Estrogen:
    The researchers found that when the patient pregnant , MS seizure frequency reduction , especially in late pregnancy , but also in production within a few months after the attack. The fetus in the mother during pregnancy can be considered a foreign object , in order to smooth the fetus in the mother survive the womb of the immune system has made ​​some adjustments. Based on these observations , to infer that estrogen may mediate the immune system is one of the hormones . There is also a small study included 12 RRMS not pregnant women , daily use of estriol 8mg, found that after six months developing MRI lesions decreased. When estriol after disabling , lesion number has increased . Despite its estriol treatment of MS theory, but to use in MS patients , which can cause endometrial hyperplasia , breast cancer, vascular effects on the heart , are to be included in the next major experimental considerations .
 Conclusion:
    MS is a disease requiring long-term war , so in addition to the development of therapeutic efficacy , but also need to consider the long-term safety and convenience .