How is MS Treated? There is as yet no cure for MS. Many patients do well with no therapy at all, especially since many medications have serious side effects and some carry significant risks. Naturally occurring or spontaneous remissions make it difficult to determine therapeutic effects of experimental treatments; however, the emerging evidence that MRIs can chart the development of lesions is already helping scientists evaluate new therapies. Until recently, the principal medications physicians used to treat MS were steroids possessing anti-inflammatory properties; these include adrenocorticotropic hormone (better known as ACTH), prednisone, prednisolone, methylprednisolone, betamethasone, and dexamethasone. Studies suggest that intravenous methylprednisolone may be superior to the more traditional intravenous ACTH for patients experiencing acute relapses; no strong evidence exists to support the use of these drugs to treat progressive forms of MS. Also, there is some indication that steroids may be more appropriate for people with movement, rather than sensory, symptoms. While steroids do not affect the course of MS over time, they can reduce the duration and severity of attacks in some patients. The mechanism behind this effect is not known; one study suggests the medications work by restoring the effectiveness of the blood/brain barrier. Because steroids can produce numerous adverse side effects (acne, weight gain, seizures, psychosis), they are not recommended for long-term use. One of the most promising MS research areas involves naturally occurring antiviral proteins known as interferons. Two forms of beta interferon (Avonex and Betaseron) have now been approved by the Food and Drug Administration for treatment of relapsing-remitting MS. A third form (Rebif) is marketed in Europe. Beta interferon has been shown to reduce the number of exacerbations and may slow the progression of physical disability. When attacks do occur, they tend to be shorter and less severe. In addition, MRI scans suggest that beta interferon can decrease myelin destruction. Investigators speculate that the effects of beta interferon may be due to the drug's ability to correct an MS-related deficiency of certain white blood cells that suppress the immune system and/or its ability to inhibit gamma interferon, a substance believed to be involved in MS attacks. Alpha interferon is also being studied as a possible treatment for MS. Common side effects of interferons include fever, chills, sweating, muscle aches, fatigue, depression, and injection site reactions. Scientists continue their extensive efforts to create new and better therapies for MS. Goals of therapy are threefold: to improve recovery from attacks, to prevent or lessen the number of relapses, and to halt disease progression. Some therapies currently under investigation are discussed below. Immunotherapy As evidence of immune system involvement in the development of MS has grown, trials of various new treatments to alter or suppress immune response are being conducted. These therapies are, at this time, still considered experimental. Results of recent clinical trials have shown that immunosuppressive agents and techniques can positively (if temporarily) affect the course of MS; however, toxic side effects often preclude their widespread use. In addition, generalized immunosuppression leaves the patient open to a variety of viral, bacterial, and fungal infections. Over the years, MS investigators have studied a number of immunosuppressant treatments. Among the therapies being studied are cyclosporine (Sandimmune), cyclophosphamide (Cytoxan), methotrexate, azathioprine (Imuran), and total lymphoid irradiation (a process whereby the MS patient's lymph nodes are irradiated with x-rays in small doses over a few weeks to destroy lymphoid tissue, which is actively involved in tissue destruction in autoimmune diseases). Inconclusive and/or contradictory results of these trials, combined with the therapies' potentially dangerous side effects, dictate that further research is necessary to determine what, if any, role they should play in the management of MS. Studies are also being conducted with the immune system modulating drugs linomide (Roquinimex), cladribine (Leustatin), and mitoxantrone. Two other experimental treatments - one involving the use of monoclonal antibodies and the other involving plasma exchange, or plasmapheresis - may have fewer dangerous side effects. Monoclonal antibodies are identical, laboratory-produced antibodies that are highly specific for a single antigen. They are injected into the patient in the hope that they will alter the patient's immune response. Plasmapheresis is a procedure in which blood is removed from the patient, and the plasma is separated from other blood substances, which may contain antibodies and other immmunologically active products. These other blood substances are discarded and the plasma is then transfused back into the patient. Because their worth as treatments for MS has not yet been proven, these experimental treatments remain at the stage of clinical testing. Bone marrow transplantation (a procedure in which bone marrow from a healthy donor is infused into patients who have undergone drug or radiation therapy to suppress their immune system so they will not reject the donated marrow) and injections of venom from honey bees are also being studied. Each of these therapies carries the risk of potentially severe side effects. Therapy to Improve Nerve Impulse Conduction Because the transmission of electrochemical messages between the brain and body is disrupted in MS, medications to improve the conduction of nerve impulses are being investigated. Since demyelinated nerves show abnormalities of potassium activity, scientists are studying drugs that block the channels through which potassium moves, thereby restoring conduction of the nerve impulse. In several small experimental trials, derivatives of a drug called aminopyridine temporarily improved vision, coordination, and strength when given to MS patients who suffered from both visual symptoms and heightened sensitivity to temperature. Possible side effects of these therapies include paresthesias (tingling sensations), dizziness, and seizures. Therapies Targeting an Antigen Trials of a synthetic form of myelin basic protein, called copolymer I (Copaxone), have shown promise in treating people in the early stages of relapsing-remitting MS. Copolymer I, unlike so many drugs tested for the treatment of MS, seems to have few side effects. Recent trial data indicate that copolymer I can reduce the relapse rate by almost one third. In addition, patients given copolymer I were more likely to show neurologic improvement than those given a placebo. The Food and Drug Administration has made the drug available to people with early relapsing-remitting MS through its "Treatment IND" program and is currently reviewing data from a large-scale study to determine whether or not to approve the drug for marketing. Investigators are also looking at the possibility of developing an MS vaccine. Myelin-attacking T cells were removed, inactivated, and injected back into animals with experimental allergic encephalomyelitis (EAE). This procedure results in destruction of the immune system cells that were attacking myelin basic protein. In a couple of small trials scientists have tested a similar vaccine in humans. The product was well-tolerated and had no side effects, but the studies were too small to establish efficacy. Patients with progressive forms of MS did not appear to benefit, although relapsing-remitting patients showed some neurologic improvement and had fewer relapses and reduced numbers of lesions in one study. Unfortunately, the benefits did not last beyond two years. A similar approach, known as peptide therapy, is based on evidence that the body can mount an immune response against the T cells that destroy myelin, but this response is not strong enough to overcome the disease. To induce this response, the investigator scans the myelin-attacking T cells for the myelin-recognizing receptors on the cells' surface. A fragment, or peptide, of those receptors is then injected into the body. The immune system "sees" the injected peptide as a foreign invader and launches an attack on any myelin-destroying T cells that carry the peptide. The injection of portions of T cell receptors may heighten the immune system reaction against the errant T cells much the same way a booster shot heightens immunity to tetanus. Or, peptide therapy may jam the errant cells' receptors, preventing the cells from attacking myelin. Despite these promising early results, there are some major obstacles to developing vaccine and peptide therapies. Individual patients' T cells vary so much that it may not be possible to develop a standard vaccine or peptide therapy beneficial to all, or even most, MS patients. At this time, each treatment involves extracting cells from each individual patient, purifying the cells, and then growing them in culture before inactivating and chemically altering them. This makes the production of quantities sufficient for therapy extremely time consuming, labor intensive, and expensive. Further studies are necessary to determine whether universal inoculations can be developed to induce suppression of MS patients' overactive immune systems. Protein antigen feeding is similar to peptide therapy, but is a potentially simpler means to the same end. Whenever we eat, the digestive system breaks each food or substance into its primary "non-antigenic" building blocks, thereby averting a potentially harmful immune attack. So, strange as it may seem, antigens that trigger an immune response when they are injected can encourage immune system tolerance when taken orally. Furthermore, this reaction is directed solely at the specific antigen being fed; wholesale immunosuppression, which can leave the body open to a variety of infections, does not occur. Studies have shown that when rodents with EAE are fed myelin protein antigens, they experience fewer relapses. Data from a small, preliminary trial of antigen feeding in humans found limited suggestion of improvement, but the results were not statistically significant. A multi-center trial is being conducted to determine whether protein antigen feeding is effective. Cytokines As our growing insight into the workings of the immune system gives us new knowledge about the function of cytokines, the powerful chemicals produced by T cells, the possibility of using them to manipulate the immune system becomes more attractive. Scientists are studying a variety of substances that may block harmful cytokines, such as those involved in inflammation, or that encourage the production of protective cytokines. A drug that has been tested as a depression treatment, rolipram, has been shown to reduce levels of several destructive cytokines in animal models of MS. Its potential as a therapy for MS is not known at this time, but side effects seem modest. Protein antigen feeding, discussed above, may release transforming growth factor beta (TGF), a protective cytokine that inhibits or regulates the activity of certain immune cells. Preliminary tests indicate that it may reduce the number of immune cells commonly found in MS patients' spinal fluid. Side effects include anemia and altered kidney function. Interleukin 4 (IL-4) is able to diminish demyelination and improve the clinical course of mice with EAE, apparently by influencing developing T cells to become protective rather than harmful. This also appears to be true of a group of chemicals called retinoids. When fed to rodents with EAE, retinoids increase levels of TGF and IL-4, which encourage protective T cells, while decreasing numbers of harmful T cells. This results in improvement of the animals' clinical symptoms. Remyelination Some studies focus on strategies to reverse the damage to myelin and oligodendrocytes (the cells that make and maintain myelin in the central nervous system), both of which are destroyed during MS attacks. Scientists now know that oligodendrocytes may proliferate and form new myelin after an attack. Therefore, there is a great deal of interest in agents that may stimulate this reaction. To learn more about the process, investigators are looking at how drugs used in MS trials affect remyelination. Studies of animal models indicate that monoclonal antibodies and two immunosuppressant drugs, cyclophosphamide and azathioprine, may accelerate remyelination, while steroids may inhibit it. The ability of intravenous immunoglobulin (IVIg) to restore visual acuity and/or muscle strength is also being investigated. Diet Over the years, many people have tried to implicate diet as a cause of or treatment for MS. Some physicians have advocated a diet low in saturated fats; others have suggested increasing the patient's intake of linoleic acid, a polyunsaturated fat, via supplements of sunflower seed, safflower, or evening primrose oils. Other proposed dietary "remedies" include megavitamin therapy, including increased intake of vitamins B12 or C; various liquid diets; and sucrose-, tobacco-, or gluten-free diets. To date, clinical studies have not been able to confirm benefits from dietary changes; in the absence of any evidence that diet therapy is effective, patients are best advised to eat a balanced, wholesome diet. Unproven Therapies MS is a disease with a natural tendency to remit spontaneously, and for which there is no universally effective treatment and no known cause. These factors open the door for an array of unsubstantiated claims of cures. At one time or another, many ineffective and even potentially dangerous therapies have been promoted as treatments for MS. A partial list of these "therapies" includes: injections of snake venom, electrical stimulation of the spinal cord's dorsal column, removal of the thymus gland, breathing pressurized (hyperbaric) oxygen in a special chamber, injections of beef heart and hog pancreas extracts, intravenous or oral calcium orotate (calcium EAP), hysterectomy, removal of dental fillings containing silver or mercury amalgams, and surgical implantation of pig brain into the patient's abdomen. None of these treatments is an effective therapy for MS or any of its symptoms. Drugs Used to Treat Multiple Sclerosis Drugs currently available to patients Steroids Adrenocorticotropic hormone (ACTH) Prednisone Prednisolone Methylprednisolone Betamethasone Dexamethasone Interferons Beta interferons (Avonex, Betaseron) Beta interferon (Rebif)-available in Europe only. Some experimental therapies Alpha interferon Cyclosporine (Sandimmune) Cyclophosphamide (Cytoxan) Methotrexate Azathioprine (Imuran) Linomide (Roquinimex) Cladribine (Leustatin) Mitoxantrone Aminopyridine, derivatives of Copolymer I (Copaxone) Rolipram Interleukin 4 (IL-4) Retinoids Total lymphoid irradiation Monoclonal antibodies Plasma exchange or plasmapheresis Bone marrow transplantation Peptide therapy Various MS vaccines Protein antigen feeding Transforming growth factor beta (TGF) Intravenous immunoglobulin (IVIg)