Multiple Sclerosis (MS)

Contents of this Article

Therapy to Improve Nerve Impulse Conduction

Because the transmission of electrochemical messages between the brain and body is disrupted in Multiple Sclerosis (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 Multiple Sclerosis (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), were successful, leading the FDA to approve the agent for the treatmernt of relapsing-remitting Multiple Sclerosis (MS). Copolymer I, unlike so many drugs tested for the treatment of Multiple Sclerosis (MS), has few side effects, and studies indicate that the agent can reduce the relapse rate by almost one third. In addition, patients given copolymer I are more likely to show neurologic (having to do with the nerves or the nervous system) improvement than those given a placebo.

Investigators are also looking at the possibility of developing an Multiple Sclerosis (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 Multiple Sclerosis (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, Multiple Sclerosis (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 Multiple Sclerosis (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 Multiple Sclerosis (MS). Its potential as a therapy for Multiple Sclerosis (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 Multiple Sclerosis (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 Multiple Sclerosis (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 Multiple Sclerosis (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 Multiple Sclerosis (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
Multiple Sclerosis (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 Multiple Sclerosis (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
• Surgical implantation of pig brain into the patient's abdomen

None of these treatments is an effective therapy for Multiple Sclerosis (MS) or any of its symptoms.

References:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
January 23, 2008
www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm

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