Student Disease Paper (Histology BIOL 315)
This sample paper earned a score of 48/50: The student included a satisfactory description of the disease and its histological effects, as well as a brief discussion of the molecular cause of the disease. The information was arranged in a logical manner with minimal spelling and grammar errors, and the student included appropriate references.
Lou Gehrig’s disease, named for the New York Yankees first baseman, but officially known as amyotrophic lateral sclerosis (ALS), is a disease that attacks the neurons in the brain and spinal cord. “Amyotrophic” means “no muscle nourishment”, “Lateral” identifies the part of the spinal cord in which the neurons die, and “Sclerosis” indicates “hardening”, therefore all together this results in degeneration of the cells and then scarring, or hardening, of the affected area (1). ALS is a steadily, and generally, a rapidly progressive neurodegenerative disease. As it attacks the function of neurons in the brain and spine that control motor function, this disease is ultimately terminal, because it eventually makes it impossible to breath without aid. Typically the disease is fatal within 3 to 5 years of the start of symptoms, though 10 percent may live through 10 years or more (2). One such case of an individual who has survived long is Stephen Hawking, who has had ALS since he was twenty-one (3), and even after 40 years with the disease he is still a major asset to key areas of physics research (1). This shows how ALS affects the nervous system, it does not interfere with brain function and thus leaves individuals fully aware of their deteriorating body (1).
The symptoms of ALS start off mildly. So much so that it is not always picked up until it has progressed. These early symptoms involve twitching, muscle stiffness, muscle weakness in a limb, or difficulty speaking clearly, chewing, or swallowing. As the weakness and atrophy advance, ALS is suspected (2). There is no trend in determining which area will be affected first. Once the disease begins in one area it spreads to other areas of the body as it advances. Through the progression of the disease individuals have greater difficulty swallowing or formulating speech. Identifying symptoms of both upper and lower motor neuron association is important in accurately diagnosing ALS. Symptoms of affected upper motor neurons include muscle stiffness and tightness, and hyperreflexia, exaggerated reflexes. A patient with ALS will display both upper motor neuron degeneration symptoms, and lower, which are atrophy and weakness of the muscles, cramps, and muscle twitches (2). While there may be other causes for the symptoms, even when there are symptoms expressed by both upper and lower motor nerve degeneration, if that cause cannot be identified, the symptoms are attributed to ALS. It is not easy to diagnose ALS because there are so many other causes that can explain symptoms due to nerve degeneration.
Determining the severity or rate of progression of the disease is vital for establishing whether appropriate help is being administered to the patient or verifying the effectiveness of treatment. A common instrument used is the ALS Functional Rating Scale (ALSFRS). This scale is a measure of 10 areas: speech, writing, salivation, swallowing, feeding, stairs, self-care, walking, respiration, bed, each is scaled from incapable, [0], to normal, [4] (4). While ALSFRS is the preferred instrument, other commonly used ones are the Barthel Index, Rehabilitation Activities Profile, Functional Independence Measure, and the Frenchay Activities Index.
Determining what causes ALS can be important in developing treatment for the disease. It generally affects persons aged 40 to 60 years and is more prominent in men than in women. At this time there is not a known direct cause of ALS5, though there is extensive research being conducted into discovering causes. Approximately 5,000 people are diagnosed in the United States with ALS each year and about 20,000 individuals have it. While in the majority of cases ALS seems to occur randomly, up to 10 percent are genetically linked and therefore inherited (2). One such genetic link is a gene the codes for the enzyme superoxide dimutase (SOD1). This enzyme protects neurons from free radicals and scientist have recognized approximately 100 mutations affecting the gene that codes for SOD1. These genetic causes only account for 2 percent of ALS cases, though they are the closest scientist are at determining a cause (1). In studying the causes of motor neuron diseases, mice have been used specifically created to express such disease. Results in these studies show that there is a distinction between the genes de-regulated in certain mutants in motor neuron diseases (6).
The course of the disease in degeneration of the nerve cells is only recently becoming clearer. Though it was noted that certain motor neurons were more easily affected than others by ALS, it was not known why and now through research, the picture is starting to develop. Generally, ALS attacks both the lower and upper motor neurons1, beginning in the spinal cord, thus depleting nerve function from its root. Scientist determined a few methods that could be to blame for the damage of motor nerve cells. Several of these include “excitotoxicity, which means there is overindulgence in the release of glutamate in the synapse that can result in cell death, “axon strangulation”, neurofilaments block nutrients streaming down the axon due to their buildup in the axon, “enzyme activation” is where enzymes such as caspases are hyperactive and fragment the neuron cell body, “proteasome dysfunction” is caused by a degrading of proteasomes that are vital for removing waste products in the cell and this leads to an accumulation of garbage, killing the cell, finally, supporting cells, such as astrocytes and glial cells could dispense toxic elements which injure the nerve cells (1).
As motor neuron diseases tend to develop later in life, there is some connection with the aging of the nerves. The motor neurons of the body cannot regenerate or divide, therefore, the nerves you have as a child are there for life, this results in atypically old cells. From indications, it is reasonably accepted that mitochondria play a crucial part in the aging process (7). For this reason, it is believed that mitochondrial mutations have a role in the development of motoneuron diseases, like ALS. Studies have shown there to be abnormalities in mitochondria from nerve tissue biopsies taken from patients with ALS (7). It is not clear exactly what structural differences have effects on the development or cause of the disease, however, faulty respiratory cycles have been noted and it is deduced that this could lead to cell death.
Given that no cure has been discovered for ALS, all one can do is treat it. Currently there is only one FDA approved treatment and that is rilozule, which reduces the discharge of damaging chemicals that harm motor nerve cells, and by doing so promotes longer survival (1). Difficulties do not stop at simply developing drugs or synthesizing proteins to protect the motor neurons and curb their degeneration, those medications must be able to reach the brain and spinal cord. It has been proposed that viruses be used to carry the genetic blueprints for these proteins, which can then be produced in the body and transmitted where needed (1). There is still much more that needs to be researched in ALS. While there have been many breakthroughs, there is still not a cure for it, all that can be hoped for is that the progression of the disease through the nervous system is slowed or that the motor neurons are better protected from the degenerative disease. Given the delicacy of the brain-spinal cord system, pursuing research into therapies poses many problems, which may be avoided in the future.
References:
Aebischer, Patrick, Ann C. Kato. "Playing Defense Against Lou Gehrig's Disease." Scientific American. Nov 2007:86-93.
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"Amyotrophic Lateral Sclerosis Fact Sheet." National Institute of Neurological Disorders and stroke. 25 Sept 2007. National Institutes of Health. 10 Nov 2007 <http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_amyotrophiclateralsclerosis.htm>.
- Hawking, Stephen. "My Experience With ALS." About Stephen. 10 Nov 2007 <http://www.hawking.org.uk/disable/dindex.html>.
- De Groot, Imelda J. M., Marcel W. M. Post, Tineke Van Heuveln, Leonard H. Van Den Berg, Eline Lindeman. "Measurement of decline of functioning in persons with amyotrophic lateral sclerosis." Amyotrophic Lateral Sclerosis. (2006):167-172.
- "Amyotrophic Lateral Sclerosis." MedlinePlus. 2007. National Institutes of Neurological Disorders and Stroke. 10 Nov 2007 <http://www.nlm.nih.gov/medlineplus/amyotrophiclateralsclerosis.html>.
- Perrin, Florence E., Gaelle Boisset, Aurelien Lathuiliere, Ann C. Kato. "Cell death pathways differ in several mouse models with motoneurone disease." Journal of Neurochemistry. 98(2006):1959-1972.
- Lin, Micheal T., M. Flint Beal. "Mitochondrial dysfuntion and oxidative stress in neurodegenerative diseases." Nature. 443(2006):787-795.