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Multiple Sclerosis

Multiple Sclerosis Multiple Sclerosis (MS) is a chronic, often disabling disease that randomly attacks the central nervous system (brain and spinal cord). The progress, severity and specific symptoms of the disease can not be predicted; symptoms may range from tingling and numbness to paralysis and blindness. MS is a devastating disease because people live with its unpredictable physical and emotional effects for the rest of their lives. MS is a well-known disease, but poorly understood. In the United States there are approximately 200 new cases diagnosed each week; MS is a common disease and not always caused by genetics.

Therefore, I feel we all need to have a better understanding of this disease that has no cure yet. I hope to make MS more understanding in my paper. In my paper I will explain what MS is, who gets MS, what MS has to do with the metabolism, some new techniques being used to pinpoint genetic factors, what some of the symptoms of MS is, and some treatments for MS. Multiple Sclerosis Multiple sclerosis (MS) is a progressive disabling illness that affects nerve cells in the brain and spinal cord (Bernard). Under normal conditions these nerve cells are surrounded by an insulating sheath made of fatty “myelin,” which speeds the passage of nerve impulses. In MS, this myelin sheath is inflamed or damaged, disrupting nerve impulses and leaving areas of scarring (sclerosis). The disruption of nerve signals within the brain and spinal cord causes a variety of symptoms that may affect vision, sensation, and body movements.

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“These symptoms usually wax and wane through a series of relapses (episodes when symptoms suddenly get worse) alternating with remissions (periods of recovery, when symptoms improve).” (Brunnscheiler) For many patients, a long history of MS attacks over several decades leads to slowly progressing disability, but for others the disability is more rapid and severe. MS is a life-long chronic disease diagnosed primarily in young adults who have a virtually normal life expectancy. Consequently, the economic, social, and medical costs associated with the disease are significant. Estimates place the annual costs of MS in the United States in excess of $2.5 billion. (Melvin) No one knows exactly how many people have MS. It is believed that, currently, there are approximately 250,000 to 350,000 people in the United States with MS diagnosed by a physician. (Boyden) This estimate suggests that approximately 200 new cases are diagnosed each week. Also, MS is the most common nerve disease to develop in young persons after birth, and it affects over 1 million young adults worldwide.

“Close relatives of a person with MS are 8 times more likely than average to develop the disease themselves, and children of a person with MS run 30 to 50 times the average risk.” (Waxman) Most people experience their first symptoms of MS between the ages of 20 and 40, but a diagnosis is often delayed. This is due to both the transitory nature of the disease and the lack of a specific diagnostic test–specific symptoms and changes in the brain must develop before the diagnosis is confirmed. (Health Central) Although scientists have documented cases of MS in young children and elderly adults, symptoms rarely begin before age 15 or after age 60. Whites are more than twice as likely as other races to develop MS. In general, women are affected at almost twice the rate of men; however, among patients who develop the symptoms of MS at a later age, the gender ratio is more balanced. (Waxman) To understand what is happening when a person has MS, it is first necessary to know a little about how the healthy immune system works.

The immune system — a complex network of specialized cells and organs — defends the body against attacks by “foreign” invaders such as bacteria, viruses, fungi, and parasites. It does this by seeking out and destroying the interlopers as they enter the body. Substances capable of triggering an immune response are called antigens. (Hofmann) “The immune system displays both enormous diversity and extraordinary specificity.” (Hofmann) It can recognize millions of distinctive foreign molecules and produce its own molecules and cells to match up with and counteract each of them. In order to have room for enough cells to match the millions of possible foreign invaders, the immune system stores just a few cells for each specific antigen. When an antigen appears, those few specifically matched cells are stimulated to multiply into a full-scale army.

Later, to prevent this army from overexpanding, powerful mechanisms to suppress the immune response come into play. T-cells, so named because they are processed in the thymus, appear to play a particularly important role in MS. They travel widely and continuously throughout the body patrolling for foreign invaders. In order to recognize and respond to each specific antigen, each T cell’s surface carries special receptor molecules for particular antigens. T cells contribute to the body’s defenses in two major ways. “Regulatory T cells help orchestrate the elaborate immune system.

” ( Kaser) For instance, they assist other cells to make antibodies, proteins programmed to match one specific antigen much as a key matches a lock. Antibodies typically interact with circulating antigens, such as bacteria, but are unable to penetrate living cells. Chief among the regulatory T cells are those known as helper (or inducer) cells. “Helper T cells are essential for activating the body’s defenses against foreign substances. ” (Kaser) Yet another subset of regulatory T cells acts to turn off, or suppress, various immune system cells when their job is done.

Killer T cells, on the other hand, directly attack diseased or damaged body cells by binding to them and bombarding them with lethal chemicals called cytokines. ( Kaser) Since T cells can attack cells directly, they must be able to discriminate between “self” cells (those of the body) and “nonself” cells (foreign invaders). To enable the immune system to distinguish the self, each body cell carries identifying molecules on its surface. T cells likely to react against the self are usually eliminated before leaving the thymus; the remaining T cells recognize the molecular markers and coexist peaceably with body tissues in a state of self-tolerance. “In autoimmune diseases such as MS, the detente between the immune system and the body is disrupted when the immune system seems to wrongly identify self as nonself and declares war on the part of the body (myelin) it no longer recognizes.” (Hauser) Through intensive research efforts, scientists are unraveling the complex secrets of the malfunctioning immune system of patients with MS.

Components of myelin such as myelin basic protein have been the focus of much research because, when injected into laboratory animals, they can precipitate experimental allergic encephalomyelitis (EAE), a chronic relapsing brain and spinal cord disease that resembles MS. The injected myelin probably stimulates the immune system to produce anti-myelin T cells that attack the animal’s own myelin. (Leuven) Investigators are also looking for abnormalities or malfunctions in the blood/brain barrier, a protective membrane that controls the passage of substances from the blood into the central nervous system. It is possible that, in MS, components of the immune system get through the barrier and cause nervous system damage. “Scientists have studied a number of infectious agents (such as viruses) that have been suspected of causing MS, but have been unable to implicate any one particular agent.” (Mayo Clinic) Viral infections are usually accompanied by inflammation and the production of gamma interferon, a naturally occurring body chemical that has been shown to worsen the clinical course of MS.

It is possible that the immune response to viral infections may themselves precipitate an MS attack. “The genes a person inherits may help determine whether that person is at increased risk for developing MS.” ( Melvin) While there is evidence from studies that this genetic component exists, it appears to be only one factor among several. Most likely an individuals genetic blueprint ultimately determines if that individual will be susceptible to a triggering factor, which in turn initiates the autoimmune process that leads to the development of MS. In the past few years, scientists have developed a set of tools that gives them the ability to pinpoint the genetic factors that make a person susceptible to MS. “These tools are the methods of molecular geneticstechniques used to isolate and determine the chemical structure of genes.” (Colin) In the 1980s, scientists began to apply the tools of molecular genetics to human diseases caused by defects in single genes.

This work led to major advances in understanding diseases such as Duchenne muscular dystrophy and cystic fibrosis. The situation for diseases such as multiple sclerosis is more complicated. Scientists now believe that a person is susceptible to multiple sclerosis only if he or she inherits an unlucky combination of several genes. (Colin) Advances in molecular genetics and the identification of large families in which several members have MS”multiplex” MS familieshave made possible research to uncover MS susceptibility genes. “Since 1991, the National MS Society has supported an international project searching for these genes.” ( National Multiple Sclerosis Society) However, even though genetic (inherited) factors seem to play a large role in the development of MS, no single MS gene has been identified so far. Instead, scientists suspect that MS develops because of the influence of several genes acting together. Many multiplex families from throughout the world have agreed to participate in these studies. The researchers are looking for patterns of genetic material that are consistently inherited by people with MS.

These recognizable patterns are called “DNA markers.” (Melvin) When one of these markers is identified, scientists focus on that area, seeking additional markers closer to that gene. Eventually the location of that gene can be identified. This process of moving closer to the gene until it is identified has to be repeated for each of the marker regions from the multiplex families. (Melvin) By 1996, as many as 20 locations that may contain genes contributing to MS were identified, but no single gene was shown to have a major influence on susceptibility to MS. (Melvin) Research will likely find that other, as yet unidentified, genes contribute to MS.

After the location of each susceptibility gene is identified, the role that the gene plays in the immune system and neuralgic aspects of people with MS will have to be determined. Because the immune system is so involved in MS, many scientists think at least some of the susceptibility genes are related to the immune system. Already there have been reports linking some immune system genes to MS. Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS. Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS.

Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. ( Kaser) The HLA patterns of MS patients tend to be different from those of people without the disease. Investigations in northern Europe and America have detected three HLAs that are more prevalent in people with MS than in the general population. Studies of American MS patients have shown that people with MS also tend to exhibit these HLAs in combination–that is, they have more than one of the three HLAs–more frequently than the rest of the population.

Furthermore, there is evidence that different combinations of the HLAs may correspond to variations in disease severity and progression. ( Kaser) Studies of families with multiple cases of MS and research comparing genetic regions of humans to those of mice with EAE suggest that another area related to MS susceptibility may be located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11, 17, 19, and X have also been identified as possibly containing genes involved in the development of MS. (Hauser) These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene’s interactions with other genes and with the environment make an individual susceptible to MS. “In addition to leading to better ways to diagnose MS, such studies should yield clues to the underlying causes of MS and, eventually, to better treatments or a way to prevent the disease.” (Ronthal) Finding the genes responsible for susceptibility to MS may lead to the development of new and more effective ways to treat the disease. Such research could also uncover the basic cause of the disease and help predict the course of the disease in an individual.

This would make it easier for physicians to tailor therapies and provide information to help people make life decisions. Another possible benefit may be the early diagnosis of people in families where one or more member already has MS. Many physi …

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