Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.
Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.
Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.
Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.
Experimental Drugs and Treatments
A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.
Aminopyridines. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine, or AP, has been associated with mild to marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, has also produced temporary improvements in nerve conduction without harmful side effects, even when taken for several weeks. One study comparing the two drugs, however, found that AP was superior in improving walking, fatigue, and overall function. Side effects of AP are more apt to include dizziness and confusion. DAP may cause abdominal pain, numbness, or tingling. Overdose can occur at relatively low doses in both drugs and may cause epileptic seizures.
Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.
Estrogen. Although estrogen is commonly associated with heightened immune factors, some autoimmune diseases, including multiple sclerosis, improve during pregnancy when levels of estriol, a form of estrogen, are high. (Estriol levels are low at other times.) In one small study, estriol treatment was associated with significantly fewer lesions and less disease activity in patients with relapsing-remitting MS. Long-term use may have adverse effects, however, and further research is needed.
T-Cell Modulators. Teriflunomide is being investigated for treating multiple sclerosis with relapse. Although many multiple sclerosis drugs are injected, teriflunomide is taken by mouth. In 2006, a phase II trial of teriflunomide showed promising results in preventing relapses and reducing the number of brain lesions (damaged tissue). Teriflunomide appears to affect the response of the immune system’s T cells.
Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small investigative studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.
Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).
Stem Cell Transplantation. Some investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that it may slow progression, although at this point it is not a cure.
Statins. Statins (medically referred to as HMG-CoA reductase inhibitors) are currently the most important drugs for lowering cholesterol. They are also showing possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis. In one 2002 study, the statin atorvastatin (Lipitor) improved MS symptoms in mice. Other statins include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and fluvastatin (Lescol).
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