Acyclovir ZoviraxMD

Acyclovir (ZoviraxMD) antiviral and other Could be a viral infection to play an etiologic role in the pathogenesis of MS. This assumption was the basis used to achieve a double-blind, drugs, and random acyclovir in the treatment of herpes infections. Patients who received sixty RRMS acyclovir (800 mg) or placebo administered three times per day. Treatment was associated with activity has been reduced 34 percent. Percent in annual relapse rate, which confirms the value of further research and related vehicles acyclovir. In a recent study of magnetic resonance imaging (MRI) data on disease activity and showed no obvious effect valaciclovir, although positive results can not be denied in the subsets of September rights

Cortical, Plasma

Produced treatment for long periods of time with corticosteroids any positive effect on the development of disability and frequency of relapses. Moreover, it can cause serious side effects including osteoporosis aseptic bone necrosis, proximal muscle weakness and high blood pressure, high blood sugar and cataracts, and mental disorders. Said recently that intravenous corticosteroids monthly may slow the progression of disability and associated interferon beta-1b, corticosteroids can reduce the production of antibodies.

A Canadian study in a large, multi-center, placebo-controlled, for a period of two years, we have shown. Value in the treatment of plasma MS were obtained deficit reduction to present themselves with a combination therapy with plasma and oral prednisone and cyclophosphamide with placebo and plasma Sham.

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Interferon Alpha

How IFN beta, alpha IFN type of IFN 1 (see the section on beta IFN). Because both of the same receptors Substances Act, it is reasonable to IFN alpha has a positive effect on the development of MS. The first large-scale clinical trials of recombinant interferon alpha, based on 98 patients for a year in the randomized double-blind protocol, has shown placebo-controlled followed, focused, great benefits.

A study recently conducted in Italy, where 20 patients MRI within six months. Found that new or improved pest were more frequent in the second set, and the frequency of relapses. This study of alpha IFN doses higher than previous studies in the management of every two days focused by intramuscular injection.

Sulfasalazine

sulfasalazine and is a safe, well-established, and endowed with well-known anti-inflammatory and immune that was used for decades in the treatment of inflammatory diseases of the intestine. Was later discovered to have a positive effect on rheumatoid arthritis. Recently, we published the results of a collaborative study of the third stage, double-blind, placebo-controlled study from the Mayo Clinic, Canada's sulfasalazine in the treatment of Active MS. 99 patients were treated in the emergency percent with active MS with sulfasalazine (up to 2 g / day) or placebo, and observed for at least three years (mean follow-up 3.7 years). Although the short-term response has (2 years) preferential treatment can prevent or slow the progression of disability by the primary endpoint measure appeared (confirmed worsening EDSS one point at least for a period of consecutive examinations at intervals of 3 months).

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Home Toxic Effects

In a recently published the results of a multicenter European Phase II trial, which placebo-controlled, randomized, blind protocol.Found a significant positive impact on the frequency of relapses and the evolution of the deficit, and not accompanied by acute toxic effects. The information MRI beneficial effect on disease activity. Treatment was well tolerated. Although the results of this study led to the approval of mitoxantrone for the treatment of MS by the FDA in 2002, was not published the results in a scientific journal with peer review.

Home toxic effects of mitoxantrone is myelosuppression and cardiotoxicity dose.

Therefore, if the treatment with mitoxantrone, it is extremely important that patients who suffer from heart disease and an observer (depending on the treatment regimen used) ECG, blood and urine analysis to exclude the results on a monthly basis and an echocardiogram every six months.

Mitoxantrone

 Mitoxantrone is mediated antineoplastic agent with a strong immunological effects, including by inhibiting immune B cells and lymphocytes-T, is much less toxic anti-cancer drugs other, is the most common serious side effects cardiotoxicity. This compound is the subject of three trials for the treatment of MS in recent years.

Last placebo-controlled, randomized, conducted in Italy of 51 patients with RRMS. The treatment was to be in the 8 mg/m2 administered intravenously once a month for a year. A were measured downward trend in disease activity by evaluating clinical outcomes and magnetic resonance imaging (MRI) and shown in this study.

Conducted last placebo-controlled, randomized, with the expected duration of two years in Italy, from 51 patients with RRMS. The treatment was to be in the 8 mg/m2 administered intravenously once a month for a year. A were measured downward trend in disease activity by evaluating clinical outcomes and magnetic resonance imaging (MRI) and shown in this study.

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Cladribine (2-chlorodeoxyadenosine)

 
 Cladribine is an immunosuppressive agent that leads to the destruction of relatively selective cells (apoptosis) and because of its toxicity and cellular resistance to adenosine deaminase. Has been studied in patients who suffer from MS, and is used in the treatment of lymphoid malignancies and other autoimmune diseases.

Results after the first year of a double-blind crossover study, and placebo in 50 patients with MS-out, which was scheduled to last two years are favorable. Patients remained (measured in degrees and the total volume of neural lesion on MRI) stable or improved in patients treated with cladribine, but it became worse in patients who received placebo. These positive results have not, however, in recent randomized Phase III study in 159 patients out with MS receiving cladribine administered two different doses (and reiterates 0.7 or 2.1 mg / kg) or placebo. Topics that were monthly assessments for 12 months, and the serial number undergo evaluation of disability scores and classroom MRI. Although treatment with cladribine have a major impact in reducing lesions on MRI, there was no significant impact on the deficit. Side effects of this drug are myelosuppression and susceptibility to viral infection (including herpes zoster).

Methotrexate

Methotrexate is immune. The oral administration of a relatively low dose, effective and non-toxic in other autoimmune diseases such as rheumatoid arthritis and psoriasis. The first test showed in the treatment of MS some decline in the frequency of relapses, but no benefit in patients suffering from Multiple Sclerosis gradual.

In a recent study, 60 ambulatory patients with progressive MS, and moderate or severe disability in the methotrexate 7.5 mg per week or placebo for two years. In the group that received treatment, significantly reduced the damage in the composite endpoint (EDSS arm evaluation function), it was noted the maximum benefit of the study early.

However, this is not important treatment effect when analyzed according to the traditional endpoint and EDSS. The impact of the disease on MRI activity also marginal. This was well tolerated low-dose methotrexate and no patient treatment stalled because of adverse events. Can it be treated for long periods with methotrexate cause irritation of the mucous membranes, and gastrointestinal symptoms, liver, and pulmonary fibrosis, and myelosuppression.

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Cyclosporine A

 
Cyclosporine A is an immunosuppressive agent used to improve the effectiveness of the success rate of the heart, kidneys and liver. It has also proven to be helpful in the treatment of certain autoimmune diseases. It in a series of studies on MS, the largest of which were analyzed workforce of 547 patients suffering from Multiple Sclerosis chronic progressive, it was found that a slight decrease in the rate of disease progression and a slight increase in the time before using the wheelchair. This modest or marginal benefits, and comes at the expense of long-term toxicity (kidney weakness and high blood pressure).

Cyclophosphamide

 
Cyclophosphamide is another immunosuppressive agent used for many years in the treatment of MS. It was originally uncontrolled studies that evaluated often, but not always, and show that improvement. Product in chronic progressive MS, particularly in patients who suffer from a disability is very light at the beginning of treatment the largest study so far, multicenter showed any positive effect. Cyclophosphamide has many side effects such as hair loss, nausea, vomiting, hemorrhagic cystitis, infertility, infections and cancer. Some doctors. Cyclophosphamide also still with shock therapy in the case of patients who deteriorate quickly, citing allegations that the stability of the disease treatment requires close monitoring and ongoing patient, including blood count, liver function tests and urinalysis.

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Azathioprine

Azathioprine is an immunosuppressant used widely in the treatment of various autoimmune diseases. He was extracted from the analysis of the results of randomized trials 7 (five and two double-blind, single blind) with patients who suffer from MS 793 by oral azathioprine (1-3 mg/kg/m2) reduces the frequency of relapses and little impact very EDSS. These results have been criticized on the grounds that used a sufficient dose of azathioprine in some studies. Side effects of azathioprine toxicity, gastrointestinal tract, and blood and liver. Another risk potential long-term cancer, but in the controlled trial, case-control, short-term (less than 5 years) are not associated with significantly increased risk. Treatment requires close monitoring and ongoing patient, including blood counts and liver function tests.

Treatment with IVIG

Has large multicenter study in Europe and Canada for IVIG (1.0 g / kg / month) in secondary progressive MS. Results on the clinical and magnetic resonance imaging (MRI) is negative.
Treatment with IVIG rarely cause serious side effects. Including aseptic meningitis, kidney failure, and vascular injury and viral infections, eczema and anaphylaxis. Another potential problem associated with its use is high contrast composition of supplements on the market, confirmed by many studies.

Can exercise and in addition to the immunosuppressive effects (due to the fact that the suppression of the production of proinflammatory cytokines, or they contain antibodies to fight different styles self) promotion of IVIG leaning back, and according to some studies. However, small studies are performed at the Mayo Clinic does not support the hypothesis that IVIG can reverse neurological deficits and visual long.

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Protocol Optimization

In addition, reduces treatment nearly half the pace of setbacks has no obvious effect on the severity of the outbreak. However, it is possible that not blind protocol optimization, which may be biased study results. Unfortunately, MRI are not included in the protocol, and the book did not produce any data on changes EDSS "confirmed" the three months and six months.

In another clinical study, we investigate the effect of high doses of IVIG (2.0 g / kg / month for 6 months) to assess disease activity as measured by magnetic resonance imaging (MRI), but there was a high dropout rate due to side effects.

In double-blind study, 40 patients Israeli with RRMS random IVIG because of loading dose (0.4 mg / kg / day for 5 days), followed by enhanced access to a unique (0.4 mg / kg) or placebo, administered every two months for two years. Treatment was reduced almost 40 percent. Percent in annual relapse rate, in addition to its impact on the EDSS. However, it did not differ significantly between the two groups in total lesion load on magnetic resonance imaging (MRI) of the brain.

Intravenous Immunoglobulin

Immunoglobulins (IgG) for intravenous administration (IVIG) have different effects on the immune system.

During the first small studies that did not show multicenter study wide effectiveness convincing Australian found that the monthly management of low-dose IVIG effective and well tolerated. A group of patients 148 RRMS (EDSS 1-6) randomly into two groups, one treated with IVIG monthly dose of 0.15 to 0.20 kg / g split and the other received a placebo for two years. Was ultimately the main effects of treatment on clinical disability (as measured by the change in EDSS), and the proportion of patients who have debilitating disability, remained stable or deteriorating (difference of one point at least on EDSS). The analysis is based on the plan showed that IVIG therapy have a significant positive impact, albeit modest, in EDSS.

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Demyelinating Disease

The study showed Enyoropathologyekal MS lesions clearly that the process of demyelination occurs in the presence of inflammatory cells and cytokines. Traditionally, demyelination and inflammation MS tie (MS often known as inflammatory demyelinating disease). Research has confirmed recently. Was a significant correlation between the deficit and the clinical onset of permanent nerve cells themselves (especially on the axon)

These insights into the functioning of the immune system led to the development of therapeutic strategies, conducted consisting, for example, prevents management of anti-inflammatory cytokines in patients with MS or treatments that pro-inflammatory cytokines. However, limited ability to predict the effect of such an intervention by the complexity of the network formed by the immune system, with many interrelated factors and mechanisms that vary depending on the stage of the disease. Even more difficult than outside entity heterogeneous MS patients, and that we will see a variety of phenomena such as the masses of the destruction of the cells, and the process of demyelination with or without the participation of the principal cells work as oligodendrogliopathie 'primary.

Given our limited understanding of the pathogenesis of MS, generally or in a particular person, can not be achieved any specific therapeutic progress to be achieved at the expense of clinical trials. These tests are to be carried out on large numbers for a long time, because the path is highly variable and unpredictable disease, and the difficulty in accurately measure neurological disability.

Cytokines

Recent data show that cytokines can be divided into two categories. First. Of inflammatory cytokines, including tumor necrosis factor alpha (TNF alpha) and interferon gamma, which may direct tissue damage in MS second layer, and cytokines anti-inflammatory, including 4 - interleukin (IL-4), interleukin -10 (IL -10), and transforming growth factor beta (TGF-beta), to suppress or prevent the disease.

There are many B cells in MS plaques and close to the latter, but they are relatively rare in the cerebrospinal fluid (CSF). These are the cells to ensure local production of immune. Antibodies are immune, but in September, it's not nature made against this antigen antibodies. In an attempt to search, and students have to discover antigen antibody inconclusive so far.

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Proteases

Macrophages secrete chemicals also called proteases (myelin destruction capable), prostaglandins, free radicals, and the immune system plays a role in inflammation and function. The second type of white blood cells are smaller cells. B-cells, including the maturity occurs in the bone marrow, we have a mission to produce antibodies. T cells, and a lot of maturity in reach of the thymus.

According to T-cell growth-and metabolism, and secrete cytokines material increases are activated once in response to exposure to the antigen. These activities and job promoting the growth of the population of lymphocytes, macrophages, and blood flow, leading to the formation of tissue edema and attract other types of white blood cells all over the infiltration. Interferon gamma is one of the cytokines secreted by activated T cells and facilitate the recognition of antigen. Associated with use in the treatment of MS with an increase in the frequency of relapses.

Differences Between

However, there are significant differences between the MS EAE and chronic. Contrary to what happens in EAE, it is difficult to detect antibodies against myelin proteins in the blood of patients suffering from Multiple Sclerosis. In FP, and we know that myelin antigen or one of its components, while in September, and we do not know yet. The antigen in question and in addition to that, to prevent and suppress EAE bit by a number of medicines that do not seem effective in September

The complex immune system. Its essential components are two types of white blood cells in the contract thymus, spleen and lymph found. These cells can circulate throughout the body through the bloodstream and lymphatic system. The largest of them is called macrophages ("macro" large Greek and "phage" eat) their job is to absorb and remove foreign objects.

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