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Multiple Sclerosis (MS)
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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 MS patients who suffered from both visual symptoms and heightened sensitivity to temperature. Possible side effects of these therapies include * paresthesia (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 MS. Copolymer I, unlike so many drugs tested for the treatment of 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 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
Cytokines are powerful chemical substances secreted by T cells. Cytokines are an important factor in the production of inflammation and show promise as treatments for MS. As growing insight into the workings of the immune system gives new knowledge about the function of cytokines, 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 (IV) 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. The thymus is an organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.
- 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 MS or any of its symptoms.
Definitions For This Page - In Alphabetical Order
* Antigen
Antigen is a structure foreign to the body, such as a virus. The body usually responds to antigens by producing antibodies.
* Demyelination
Demyelination is damage caused to myelin by recurrent attacks of inflammation. Demyelination ultimately results in nervous system scars, called plaques, which interrupt communications between the nerves and the rest of the body.
* Experimental Allergic Encephalomyelitis (EAE)
Experimental Allergic Encephalomyelitis (EAE) is a chronic (lasting a long time) brain and spinal cord disease similar to MS which is induced by injecting myelin basic protein into laboratory animals.
* Immunosuppression
Pronounced - IH-myoo-noh-suh-PREH-shun
Immunosuppression is suppression of the immune system functions and its ability to fight infections and other diseases. Many medications under investigation for the treatment of Multiple Sclerosis (MS) are immunosuppressants.
* Intravenous (IV)
Pronounced - IN-truh-VEE-nus
Intravenous, or IV, usually refers to a way of giving a drug or other substance through a needle or tube inserted into or within a vein.
* Myelin
Pronounced - MY-eh-lin
Myelin is a fatty covering insulating nerve cell fibers in the brain and spinal cord, myelin facilitates the smooth, high-speed transmission of electrochemical messages between these components of the central nervous system and the rest of the body. In Multiple Sclerosis (MS), myelin is damaged through a process known as demyelination, which results in distorted or blocked signals.
* Paresthesia
Pronounced - par-es-THEE-zhuh
Paresthesia is abnormal sensations such as numbness, prickling, or "pins and needles."
* Receptor
Pronounced - reh-SEP-ter
Receptor is a protein on a cell's surface that allows the cell to identify antigens.
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References:
NIH Publication No. 96-75
September 1996
www.ninds.nih.gov
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