Metachromatic Leukodystrophy

Multiple Sclerosis (MS) is a neurologic disease that affects the Central Nervous System (CNS) through cellular immune response and the demyelination of CNS white matter (McCance et al., 2014, pp. 630–633). The initial causes of MS are unknown however, it is believed that it could possibly be due to an immune response to an initiating infection or an autoimmune response to CNS antigens on the myelin itself (Brück, 2005) (Miljković and Spasojević, 2013). MS is a result of the degradation of the myelin sheath surrounding neurons and therefore disrupts the transmission of action potentials along these cells. MS can display itself in the form of symptoms ranging from muscle weakness to trouble with sensation and coordination (NHS, 2016). The degradation of myelin leads the body to attempt to remyelinate the neurons, a process that in turn leads to the thickening of the cell by glial cells and this causes lesions to form (Chari, 2007). It is this thickening (sclerae) from which the disease gets its name. Sufferers of MS can either have a relapsing type of MS, in which there are episodes that lead to the worsening of symptoms for a period of time, or a progressive type of MS where symptoms gradually progress and worsen (McCance et al., 2014, pp. 630–633).

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS affects approximately 3.0 million people globally, with about 300,000 cases in the United States. Twice as many women as men have MS. The average ages for onset of MS is 20-40 years. In MS, cells in the immune system attack and destroy myelin, the fatty tissue surrounding nerve cells (http://www.phylomed.com/MS.html). Scar tissue replaces the myelin, interfering with the transmission of nerve signals and leading to numbness, fatigue, spasticity, loss of muscle control, and various other debilitating symptoms. There are four broad theories

Marfan syndrome is a connective tissue disorder that is caused by an increase in the production of

The breakdown of the myelin sheath is caused from a mutation of the gene that makes the Adrenoleukodystrophy protein (ALDP). This ALD protein helps the body metabolize saturated very-long-chain fatty acids found in the serum and tissues of the central nervous system. The newly mutated gene no longer acts as a help aid to breaking down the long-chain fats. Therefore, the body starts accumulating an abnormal amount of fat in the nervous system, adrenal gland and testes that sets off an unusual response in the immune system; demyelination.

Multiple Sclerosis is a disease that attacks the myelin coating over the nerve receptors in your brain and spinal cord. Myelin is a fatty material that coats and protects the nerves in your brain. These nerves send signals to the rest of your body enabling

Multiple Sclerosis, commonly known as MS is an autoimmune disease of the central nervous system. Scientists have been studying MS since the 19th century. In MS, the body’s immune system produces cells and antibodies that attack myelin in your brain which is essential for the nerves in your brain and spinal cord to conduct electricity to perform its function. The attack on myelin results in vison loss, paralysis, numbness, muscle weakness, difficulty walking, stiffness, spasms, and bladder and bowel problems. MS has varying degrees of severity and affects people between the ages of 20-50, mostly women. Although there are treatments, there is no cause and cure yet.

“Multiple sclerosis (MS) is a disease in which your immune system attacks the protective sheath (myelin) that covers your nerves” (Mayo Clinic). The immune system is a defensive system that protects your body from diseases and illnesses such as parasites and bacteria (Science Museum). Not only does your immune system defend the human body but also the immune system can work against the body, which is known as autoimmune disease. Since the immune system is working against your body to attack the myelin, this creates an opportunity for multiple sclerosis to invade the nerves in the central nervous system (CNS). The myelin within the body acts like insulation to protect and coat the nervous system (National Multiple Sclerosis Society). Once the myelin is eroded, the nerves become exposed which then causes signals to and from the brain to become distorted or irrupted causing a wide range of symptoms to occur (National Multiple Sclerosis Society). The effect of the myelin eroding is an irreversible process (Mayo Clinic). “The damaged myelin forms scar tissue (sclerosis), which

Then there is the theory that common diseases or STD's trigger MS and this initiates the migration of white blood cells to enter the brain. Once in the brain these white blood cells activate certain parts of the immune system and thus the immune system begins to attack the myelin that surrounds the nerve. (1) There is another theory that the scarring of the myelin of the nerve is caused by oxidation injury. (3) Oxidation injury is seemingly caused by unstable molecules named free radicals. These free radicals supposedly take electrons from healthy molecules they find in the myelin. These free radicals are also said to occur when the body has been exposed to toxic chemicals. (5) Free radicals are described as punching holes in the cellular walls of our bodies. There is another theory that researchers of MS present. The

Multiple Sclerosis is an autoimmune disorder where the myelin sheath within the Central Nervous System is attacked (National Multiple Sclerosis Society, 2017). The myelin sheath protects the axon of the nerve cell. When the myelin sheath is intact, the axon is able to carry impulses away from the neuron’s cell body, and the message carried is clear. With Multiple Sclerosis, the myelin sheath becomes scarred, hence the word “sclerosis”, and distorts the nerve impulses traveling over the CNS (National Multiple Sclerosis Society, 2017). This may cause the message to be changed or stopped altogether.

Miller-Dieker lissencephaly syndrome (MDS). MDS features include classic lissencephaly (incomplete or absent gyration of the cerebrum), craniofacial dysmorphims, mental retardation and intractable epilepsy. MDS is a life-shortening disease, with death most often occurring during early childhood (Dobyns, W.B., Curry, C.J.R., Hoyme, H.E., Turlington, L., and Ledbetter, D.H. Clinical and molecular diagnosis of Miller-Dieker syndrome. Am. J. Hum. Genet 1991. 48, 584–594; Nagamani, S.C., Zhang, F., Shchelochkov, O.A., Bi, W., Ou, Z., Scaglia, F., Probst, F.J., Shinawi, M., Eng, C., Hunter, J.V., et al. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.

Multiple Sclerosis occurs as a result of demyelination of the axons within the central nervous system and neuronal loss.1 The immune system produces antibodies that attack oligodendrocytes. When the oligodendrocytes are destroyed, they produce patches of demyelination referred to as plaques.2 (p.41) These plaques are found in the white matter of the central nervous system. With the loss of myelination of neurons, the transmission of signals may become slowed or blocked.2(p.41) Communication between the brain, spinal cord, and other areas of the body are hindered.3 Multiple sclerosis may result in the deterioration of the myelin surrounding the nerves, and also the nerves themselves. Unfortunately, this disease process is irreversible, incurable and often debilitating.3

In 1906 a physician, named Alois Alzheimer, cared for a fifty-one year old patient with severe dementia. Upon her death, he was able to examine her brain at autopsy. Dr. Alzheimer was able to take advantage of recent innovations in microscopy and histological techniques that allowed him to study in detail the cellular components in nervous tissue. He found that the brain of his patient had severe cortical atrophy and described the neurofibrillary bundles and plaques that are now the hallmark for definitive diagnosis of what he at that time called “presenile dementia”. An account of his first patient was published in 1907. It is a little ironic that reevaluation this case has lead some to believe that this first patient did not suffer from the Alzheimer’s disease at all. Instead they believe she suffered from a different, rare disease called metachromatic leukodystrophy (Izenberg, 2000).

In the movie Lorenzo’s Oil it covers the story of a family whose son is struck with an disease called (ALD) or Adrenoleukodystrophy. ALD is a genetic disorder caused by a defect of a certain gene that is related to several related issues one is ALD. ALD only affects males, but females can only be affected by becoming a carrier for the genetic fault. ALD affects process of taking in fats like C-24 and C-26 which because they cant be taken in safely damage the myelin. The myelin acts as a protective coating around the brains nerves causing the afflicted person’s physical and mental health begin to degrade.

1. The movie Lorenzo’s Oil challenges some of the medical assumptions made around the disease Adrenoleukodystrophy (ALD). Firstly within the movie, during the initial diagnosis of the disease, Dr.Nikolais informs the family there was is cure for ALD. The Odone’s refuse to accept this fate of their son and challenge this by discovering an oil that appears to ‘cure’ ALD. Secondly within the film is it explained that with ALD, elevated very-long-chain fatty acids (VLCSFA) levels lead to deterioration of myelin sheaths around the nerves.

In conclusion the PMD is a rare, monogenic, pediatric leukodystrophy disorder. It is categorized into three forms depending on abnormality expression of the PLP1 gene affecting the myelin sheaths. Much therapeutics research is based on stem cells. Yet there is one clinical trails neural stem cell phase 1.