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Neurodegenerative Disorders

Stem Cell Therapy: A Question of Ethics

Imagine you have been diagnosed with a disease, and you are told that there is no cure. There are treatments available to help with your symptoms, but they do not guarantee your quality of life, nor how much time you have left. Your doctor tells you that there are experimental treatments available, research studies you can participate in. The study mentioned in particular involves the use of embryonic stem cells.

Medicine is no stranger to the use of stem cells. A stem cell is defined as “a cell that has the ability to continuously divide and differentiate (develop) into various other kinds of cells [or] tissues” (Barker et al., 2013). In 1956, Dr. E. Donnall Thomas performed the first bone marrow transplant in Cooperstown New York. Bone marrow is a spongy tissue found in the center of bones, and it contains cells called haematopoietic (or blood-making) stem cells. Bone marrow is usually extracted from the lower spine using a needle. To obtain embryonic stem cells, however, scientists must harvest an embryo.

Scientists learned how to harvest stem cells from embryos in 1998, and while it was a major breakthrough, controversy also sparked as a result of it. Embryonic cells have a huge potential to help cure diseases and form treatments, but they could not be obtained without “destroying human embryos”. In 2006, scientists learned how to manipulate human cells to behave like stem cells. This breakthrough could have ended the controversy, but embryonic stem cells were still needed. The manipulated cells, called pluripotent cells, are compared to embryonic stem cells to determine how well they will work. Embryonic stem cells are also used as a control group in experiments. However, the other ethical issue present is that the manipulated cells  have the potential to turn into clones of the donor. Most countries have passed laws to prevent this from happening, but it remains an ethical issue.

We now know what makes embryonic stem cell therapy so controversial, but does the end justify the mean? Is it ethical to use embryonic stem cell therapy to help treat diseases that have no known cure? What if embryonic stem cells can be used to cure diseases that were otherwise incurable? In the case of neurodegenerative disorders, there are no known cures. Doctors treat symptoms to help improve the quality of life of those who have neurodegenerative disorders. But, could stem cell therapy help reverse the damage done by the disorders?

Stem cells have been used for the purpose of replacing and restoring cells lost through neurodegeneration in patients with Parkinson’s Disease, Multiple Sclerosis, Huntington’s Disease, Motor Neuron Disease, and others (Pen et al., 2016). Trials were designed to replace dopamine cells in patients suffering from Parkinson’s Disease; many younger participants benefited, but were not protected from disease progression (Pen et al., 2016). The common thread among various neurodegenerative disorders is the atypical protein formation and the induction of cell death  (Barker et al., 2013). Stem cells, whether they are pluripotent cells that have been synthesized in a lab or embryonic stem cells, can be grown and differentiated into a relevant cell type to replace cells lost in a disease process (Barker et al., 2013). Clinical trials are not abundant because pluripotent cells, which is seemingly the more ethical of the two, are still being refined (Barker et al., 2013). In addition to this, trials have not been conducted on humans because choosing who gets to participate poses another ethical dilemma (Barker et al., 2013). Factors such as age, disease type, duration of the disease, prognosis must all be considered when determining the subject pool for a study. Neurodegenerative disorders are not identical from person to person, thereby making the recruitment process of finding individuals whose diseases and situations resemble each others quite difficult.

Stem cell transplantation has been used in closely related fields, such as spinal cord injuries. For example, patients with complete spinal cord injuries were able to improve their neurological functions with the use of stem cells without severe adverse effects, and the damage done to the white matter tracts in the spinal cords were repaired (Barker et al., 2013). This lead to improvement in transmission of signals to and activity of the muscles in their legs. This change shows that the use of stem cells holds a new potential for treatments in the spectrum of neurological diseases (Barker et al., 2013). Scientists believe the same techniques can also be applied to  diseases such as Alzheimer’s Disease and Parkinson’s Disease, hopefully, reversing the damage done by the neurodegeneration. Stem cell use in the treatment of any disease will cause ethical questions to arise, it is no different when talking about its use in the treatment of neurodegenerative disorders. Stem cells have the potential to improve quality of life, decrease the progression of disease, and maybe even cure these disorders. However, we must ask ourselves, is it benefitting the greater good?

References

Australian Cancer Research Foundation. (2017, January 17). The first bone marrow transplantation in 1956 changed cancer treatment. Retrieved November 28, 2018, from https://home.cancerresearch/1956-the-first-successful-bone-marrow-transplantation/

Barker, R. A., & Beaufort, I. D. (2013). Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain. Progress in Neurobiology,110. doi:10.1016/j.pneurobio.2013.04.003

Genetic Science Learning Center. (2014, July 10). The Stem Cell Debate: Is it Over? Retrieved November 28, 2018, from https://learn.genetics.utah.edu/content/stemcells/scissues/

Pen, A. E., & Jensen, U. B. (2016). Current status of treating neurodegenerative disease with induced pluripotent stem cells. Acta Neurologica Scandinavica,135(1). doi:10.1111/ane.12545

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Neurodegenerative Disorders

Multiple Sclerosis: A Neurodegenerative Disease

Multiple Sclerosis, more commonly known as MS, is a disease in which the body’s immune system attacks the central nervous system. The central nervous system is composed of the brain, spinal cord, and optic nerves. In individuals with MS, the immune system causes inflammation in the central nervous system that damages the myelin sheath, the protective covering of nerve fibers (also known as axons), as well as the nerve fibers themselves. The axonal destruction unfortunately causes irreversible neurological damage, which is why Multiple Sclerosis is primarily considered a neurodegenerative disorder (Ciffeli et al., 2002). Myelin is a fatty substance that surrounds, insulates, and protects the axons. Therefore, when the myelin sheath is damaged or destroyed, the central nervous system’s ability to send and receive messages is altered or stopped completely. The resulting damaged areas then develop scar tissue, which is where the disease gets its name — multiple areas of scarring or multiple sclerosis (condition of hardening or scarring).

Multiple Sclerosis is still widely regarded as a disease of the white matter in the brain, but recent evidence shows that there may be significant involvement of gray matter too (Boraschi et al., 2002). Grey matter contains nerve cell bodies, dendrites, and axon terminals of neurons (Villines, 2018). The gray matter is where all the synapses are. A synapse is the intersection between two dendrites. White matter, on the other hand, is where axons connect different areas of gray matter. Impulses are carried from the cell body through the dendrites, into the synapse. There, the axon from the receiving cell will pick up the impulse. In this process, the job of white matter is to conduct, process, and send nerve signals up and down the spinal cord. Therefore, damage to the white matter of your brain or spinal cord can affect your ability to move, use your sensory faculties, or react appropriately to external stimuli. Some people with damaged white matter may also experience deficits in reflexive reactions (Villines, 2018).

The damage to various areas of the central nervous system produces a variety of neurological symptoms that vary based on severity. Common symptoms of MS may include fatigue, numbness or tingling, difficulty walking, spasticity, and cognitive dysfunction, while less common symptoms may include speech problems, swallowing and breathing problems, tremors, seizures, and hearing loss (National Multiple Sclerosis Foundation).

While the cause of multiple sclerosis is still unknown, scientists believe it is triggered by a combination of factors. Therefore, research is ongoing in the areas of immunology (the study of the immune system), epidemiology (the study of disease patterns in large groups of people), and genetics (understanding genes that may not be functioning correctly in people who develop MS). Infectious agents are also being studied to see if there is a correlation between infections and multiple sclerosis. While there is no single risk factor that has been identified, a variety of factors are believed to contribute to the overall risk of developing multiple sclerosis.

Among these “risk factors” are geographical location, insufficient levels of vitamin D , smoking history, and obesity. For example, multiple sclerosis is known to occur more frequently in individuals who live in areas further from the equator. Data also suggests that exposure to some environmental agents before puberty may predispose an individual to develop multiple sclerosis. In addition, growing evidence has shown that low vitamin D levels are a risk factor for developing multiple sclerosis. Sunlight is a natural source of vitamin D, and areas closer to the equator are exposed to greater amounts of sunlight year-round than people living closer to the north and south poles. Another risk factor is smoking. As with many other diseases, smoking increases the risk for developing multiple sclerosis, and also increases the progression of the disease. Fortunately, the evidence also suggests that quitting smoking is associated with reduced risk and a slower progression of the disease. Lastly, childhood and adolescent obesity, particularly in females, may increase one’s risk of developing multiple sclerosis later on in life.

Although multiple sclerosis is not an inherited disease, there is a genetic risk factor associated with it. The probability of developing multiple sclerosis increases if a first degree relative (mother, father, siblings, children) has the disease. In identical twins, if one twin has the disease, the other twins risk for developing MS is about one in four. Approximately 200 genes have also been identified as contributing a small amount to the overall risk of developing multiple sclerosis, but additional research needs to be done to better understand these factors that contribute to the development of this disease.

Multiple sclerosis is thought to affect more than 2.3 million people worldwide. While the disease is not contagious or directly inherited, epidemiologists have identified factors in the distribution of MS around the world that may eventually help determine what causes the disease (National Multiple Sclerosis Foundation). These factors include gender, genetics, age, geography and ethnic background. Most people are diagnosed between the ages of 20 and 50, and although MS can occur in young children it is more prevalent in older adults. MS is at least two to three times more common in women than in men, thereby suggesting that hormones may also play a significant role in determining an individual’s susceptibility to acquiring multiple sclerosis. Overall, MS is a debilitating neurodegenerative disease that renders an individual unable to go about their day to day activities without experiencing pain and other symptoms. While no cure currently exists, there are various treatment options that can be utilized to treat the symptoms of this disease and improve one’s quality of life.

References

Boraschi, D., & Penton-Rol, G. (2016). Immune rebalancing: The future of immunosuppression. Amsterdam: Elsevier/Academic Press.

Cifelli, A., Arridge, M., Jezzard, P., Esiri, M. M., Palace, J., & Matthews, P. M. (2002). Thalamic neurodegeneration in multiple sclerosis. Annals of Neurology,52(5), 650-653. doi:10.1002/ana.10326

National Multiple Sclerosis Society. (n.d.). What Is MS? Retrieved from https://www.nationalmssociety.org/What-is-MS  

Villines, Z. (2018, August 02). Gray Matter vs. White Matter in the Brain. Retrieved from https://www.spinalcord.com/blog/gray-matter-vs-white-matter-in-the-brain

 

Categories
Neurodegenerative Disorders

You Are What You Eat: The Role of Nutrition in Neurodegenerative Disorders

In my elementary school cafeteria, there was a poster right at the front of the lunch line. It was a “Got Milk” poster. When I went to middle school and high school, I found the same poster in the same spot. I grew up learning how important it was to eat my vegetables, and spent days watching Rachel Ray teach parents how to “trick” their kids into eating brussels sprouts and broccoli.

Our mindsets have changed since the fast food craze of the 1950’s. More notably in the recent years, our culture is starting to shift away from McDonald’s and Burger King towards healthy grocery stores like Whole Foods and Trader Joe’s. If you walk into a grocery store in 2018, words like “vegan”, “non-GMO”, “organic”, “gluten-free”,”soy-free” and “dairy-free”are not uncommon, which wasn’t the case a mere 15 years ago. Today, the government has even launched a campaign promoting water over juices and soft drink. Why is all of this important? We are told eating healthy and exercising is good for us. But, is it so good that it can prevent and/or delay neurodegenerative disorders?

The brain is an organ, and as any other organ it needs nutrients to build and maintain its structure. It needs to function harmoniously and protect itself from premature aging and diseases. Neurological development can be compromised in the presence of dietary deficiencies. For example, iron misregulation and accumulation in the brain is a possible cause for neurodegenerative disorders (Ke, et al, 2003). The brain needs nearly all nutrients; but, too many of the wrong vitamins and minerals can be harmful as well. Diet and exercise together can reduce age-related cognitive decline and the risk of neurodegeneration (Ke, et al, 2003).

A study conducted in Spain formulated a link between diet, inflammation, and neurodegeneration. Inflammation is a the body’s natural response an injury, to defend against foreign invaders, and to repair damaged tissue. Essentially, the body uses inflammation to heal itself, and it is beneficial to us. Inflammation is supposed to last a few days: the process is not instant. But when it lasts longer than the required time to heal, it causes a state of chronic low-grade inflammation, which may trigger the development of several diseases and disorders  by activating the body’s immune response (Wärnberg et al, 2009).

For many years, the brain was regarded as an organ that was not susceptible to inflammation and immune responses. Now we know this is not true (Wärnberg et al, 2009).

Neuroimmunomodulation, the study of inflammation and the nervous system, is a rapidly expanding field of research (Wärnberg et al, 2009). Multiple Sclerosis, or M.S., is a neurodegenerative disease characterized by inflammation that damages the myelin sheath, the protective coating on nerve fibers (National Multiple Sclerosis Society, n.d.). Recently it has been suggested that inflammation also plays a role in Alzheimer’s disease, HIV-related dementia, and memory loss after traumatic brain injury because it involves a substantial loss of nerve cells (Wärnberg et al, 2009).

Wärnberg and his fellow researchers suggest that following a healthy diet has a “dual effect on both reducing inflammation and meliorating neurodegenerative disorders,” (Wärnberg et al, 2009). Foods like grapes, apples, berries, pomegranates, and green tea are rich in antioxidant compounds that have anti-inflammatory properties and other related health benefits. Green tea aids in boosting metabolism, and apples contain fiber which is good for digestive health. Although the number of studies describing a link between foods and inflammation is low, the available evidence indicates that consuming vegetables and fruits, an antioxidant rich diet or vitamins, fiber, and magnesium aid in reducing inflammation. Wärnberg mentions that dietary and lifestyle pattern as a whole is more important than focusing on consuming a single nutrient (2009).

Chronic low grade inflammation can also be related to obesity, even at early ages. Other unhealthy habits, such as the “Western Dietary Pattern”, smoking and drinking, can also be linked  to chronic low-grade inflammation (Wärnberg et al, 2009). The “Western Dietary Pattern” is characterized as being high in refined sugars, starches, saturated fats, trans-fat, and poor in natural antioxidants and fibers from fruits, vegetables, and whole grains. Processed food increases inflammation level in the body, leading to chronic low-grade inflammation. The ideal lifestyle that would satisfy all strategies to reduce inflammation in the body would be characterized by no tobacco use, moderate physical activity, and a high intake of fruits, vegetables, legumes, whole grains, olive oil, and fish.

The Mediterranean diet is mentioned by name and is associated with a lower risk of several forms of cancer, obesity, high cholesterol, high blood pressure, diabetes, heart disease, overall mortality, and reduced levels of inflammatory markers (Wärnberg et al, 2009). The U.S. News lists the Mediterranean Diet as number one in the “Best Diets Overall” category and scores it 4.1 out of 5 stars. There is no calorie counting involved in this diet. Simply put, it involves eating more fruits, vegetables, whole grains, beans, nuts, olive oil, herbs and spices, red wine, and eating fish or seafood at least twice a week (Mediterranean Diet, n.d.). It advises to consume poultry (chicken), eggs, cheese, and yogurt in moderation, while sweets and red meat should be saved for special occasions. Moderate exercise is also advised (Mediterranean Diet, n.d.). This diet is not necessary to reduce inflammation, but a lot of the “do eats” overlap with the list of foods that fit in the ideal diet to reduce inflammation.

Fast food made it convenient and inexpensive to eat, but it wreaks havoc on our bodies. It may be costly and more inconvenient to eat healthy, but it truly has its benefits. What you put in your mouth matters. Eating nutritious foods will keep your body in balance and reduce the risk for many diseases and disorders, premature aging, and add to your quality of life. Incorporating healthier foods into your existing lifestyle is an excellent way to start implementing change. Overall, eating a well-balanced diet and avoiding processed foods reduces the amount of chronic low-grade inflammation in the body, which can prevent or delay the onset of neurodegenerative disorders such as Multiple Sclerosis and Alzheimer’s disease.

References

Ke, Y., & Qian, Z. M. (2003). Iron misregulation in the brain: A primary cause of neurodegenerative disorders. The Lancet Neurology, 2(4), 246-253. doi:10.1016/s1474-4422(03)00353-3

Mediterranean Diet. (n.d.). Retrieved from https://health.usnews.com/best-diet/mediterranean-diet

National Multiple Sclerosis Society. (n.d.). Definition of MS. Retrieved from https://www.nationalmssociety.org/What-is-MS/Definition-of-MS 

Wärnberg, J., Gomez-Martinez, S., Romeo, J., Díaz, L., & Marcos, A. (2009). Nutrition, Inflammation, and Cognitive Function. Annals of the New York Academy of Sciences, 1153(1), 164-175. doi:10.1111/j.1749-6632.2008.03985.x