Amyotrophic Lateral Sclerosis Report
I. Illness in Question
Amyotrophic lateral sclerosis is a progressive, chronic disease of unknown etiology. It affects motor areas of the cerebral cortex, axons of upper motor neurons in the lateral white columns, and lower motor neurons which are in the spinal cord and brainstem. Motor neurons are responsible for ultimately directing muscle movement, a relay signal travels from the brain or spinal cord to the muscles. ALS often begins in sections of the spinal cord that serve the hands and arms but spreads to involve the entire body and face, without affecting intellect or the tactile sense.
Symptoms and signs
The early signs and symptoms of ALS may seem vague as they vary significantly from patient to patient, and the prolongation of the disease. They include fasciculations (muscle cramping and twitching), atrophy, fatigue, shortness of breath, slurred speech or difficulty in articulating speech, emotional lability, hyporeflexia (diminished reflexes) or hyperreflexia (amplified reflexes), weight loss and shortness of breath even at rest.
Impact on body organs and tissues
Affected individuals limb muscles develop spasticity, they lose strength and the ability to move their arms and legs, as a result, the capability to control voluntary movement can be lost. Adding to this, approximately 75 percent of people with ALS will develop weakness and deteriorating of the bulbar muscles, which control speech, swallowing and chewing.
ALS affects the alveoli in the circulatory system as it can hinder a patients breathing by debilitating the respiratory muscles that are crucial for breathing. As the respiratory muscles weaken, oxygen cannot be exchanged, and an excess of carbon dioxide builds up in the bloodstream this is called acidosis. This explains why people with ALS often have trouble in swallowing and fatigue.
NEED ONE MORE AFFECT
Age of onset
ALS has a peak onset of 55 to 65 years.
The average survival is 2 to 3 years from diagnosis, with 25% of patients surviving 5 years, and 5 to 10% surviving 10 years postdiagnosis.
II. The function of Superoxide Dismutase (SOD1)
This enzyme is found in all living cells, primarily in the cytoplasm. It plays an essential role in human cells, by breaking down unstable free radicals in the body and converts them into molecular oxygen (O2) and hydrogen peroxide (H2O2), both of which are very stable molecules. It can perform this reaction due to its catalytic copper atom that acts and an electron donator and acceptor to superoxide.
The catalytic reaction takes place within cells:
2 superoxide + 2H+ ? O2 + H2O2
The mutations in SOD1 aggravates a gain of new toxic properties.
III. 4 ways in which mutated SOD1 may contribute to the impairment of the function of motor neurons
SOD1 proteins may aggregate in the axon to form a large clump. These intracellular aggregates may interfere with other proteins whose function is to maintain cell health or inhibit proteasomal breakdown of damaged regulatory proteins leading to the accumulation of cellular waste resulting in an increase in toxicity levels within cells that most likely will result in the lysosomes and proteasomes provoking apoptosis.
SOD1 impairment results in oxidative stress that diminishes the function of the mitochondria.
SOD1 mutants diminish the function of oligodendrocytes in the central nervous system.
The SOD1 mutation results in the reduced expression of vesicular Ach transporter (VAChT) protein, involved in the packaging of Ach inside the synaptic vesicles before release.
IV. Testing blood glucose concentrations and its implications in terms of Type II diabetes
How a dipstick works
A dipstick analysis is a semi quantitative method of determining the blood glucose concentration in a sample of urine. A dipstick is a reagent strip containing the immobilised enzymes; glucose oxidase and peroxidase and chromogen at one end. The strip is lowered into a sample of urine. Glucose oxidase catalyzes the oxidation of glucose into gluconic acid and reduces oxygen to hydrogen peroxide. Hydrogen peroxide in the presence of peroxidase will oxidise the chromogen, and thus resulting in a colour change. This is shown through the following reactions:
Glucose + O2 ? gluconic acid + H2O2
H2O2 + chromogen ? oxidized chromogen (new colour)
The colour produced is matched against a chart, the intensity of the colour gives information about the concentration of glucose present. A fixed time should be used for the test pads to develop for instance, 60 seconds, to ensure that the result will not be falsely elevated.
The link between Glucosuria and Type II diabetes
Glucosuria is the term given when glucose is present in the urine, it is usually caused by hyperglycemia (increased glucose in the blood). For a healthy adult, approximately 180g of glucose is filtered by the glomerulus every day, under normal circumstances 1% of the 180g is being excreted in the urine, the remaining 178.2g is reabsorbed back into the bloodstream.
V. Why gene therapy is not a possible option to treat ALS
Idiopathic nature of the disease
Rarity of the disease makes it challenging to discover genetic lesions as it will require a large-scale cooperation of organisations and nations.
Selection of a suitable vector for the delivery of the gene of interest
Gene therapy is difficult as most of the mutations are spontaneous and especially to to the fact that it is liked to over 40 mutations
The fundamental aspect is the isolation of the gene mutation.
VI. Potential advantages and disadvantages of testing for the SOD1 mutation
Individuals who are found not to carry the mutant SOD1 gene, where the harmful gene is known to run in their family may feel that they are less anxious and as a result can have a better quality of life; following this, test results enables one to make decisions about starting a family especially if a person and their partner is a carrier of the disease, doctors will be able to determine the likelihood of their baby having the genetic condition.
VII. Need a title
Although John’s father possesses the same mutation he has not developed ALS this may be because of the following reasons:
• ALS may be inherited in an autosomal dominant pattern, this is where the affected individual has one copy of the mutant gene and the other, a normal gene both on a pair of autosomal chromosomes. Which means that one copy of the mutant gene in each cell is adequate to cause the disorder.
• ALS may be inherited in an autosomal recessive way, this is where the affected individual has two copies of the mutant gene.
• ALS may also be inherited in X-linked inheritance, but because John’s father possesses the mutation this cannot be the case.
VIII. Why evolution has not resulted in the eradication of ALS
While there is no consensus regarding the