The Role of Autophagy in Duchenne Muscular Dystrophy - Article Example

Homeostasis The first article by De Palma et al. highlights the role played by autophagy in Duchene muscular dystrophy (DMD). According to De Palma et al. (2014) this X-linked disorder affects 1 out of every 3,500 new-borns whose dystrophin genes are mutated. The authors note that the most affected muscle in DMD is the diaphragm which undergoes wasting leading to respiratory failure and eventual death. It should be noted that both cardiac and smooth muscle are also affected. Dystrophin is vital in the maintenance of muscle membrane integrity. It forms a complex that is vital to the stabilization of muscle cells during contraction (De Palma et al., 2014). Any abnormalities therefore leads to impaired muscle function as is the case in Duchene Muscular Dystrophy. De Palma et al. (2014) notes that autophagy is an essential mechanism involved in the turnover of cell components in various cellular processes. It is in essence a physiological process whose aim is to see to it that protein aggregates, cytoplasmic components and organelles are degraded. Its role in muscle has been the subject of intense research. In uncontrolled situations, autophagy has been linked to atrophy, weakness and other signs of myopathy like irregular fibre distribution (De Palma et al., 2014). Initial research indicates that dysfunctional autophagy is directly implicated in the pathogenesis of muscular dystrophy. It is important to note that recent studies in mice indicate that exercise aids in the induction of beneficial autophagy. Despite these findings, no satisfactory therapy for DMD is currently in existence (De Palma et al., 2014).The current gold standard is corticosteroid therapy which serves to delay impairment of muscle function. This therapeutic option only offers temporary relief and is associated with multiple debilitating side effects like immune suppression, obesity and bone demineralization. De Palma et al. (2014) are of the opinion that pharmacologically modulating autophagy to delay muscle degeneration offers promise. These include AMPK pharmacologic agonists, and RNPs. The authors emphasise the importance of using autophagy in combination with other therapeutic strategies like a low protein diet, cell and gene therapies in the treatment of DMD (De Palma et al., 2014). Autophagy is undoubtedly linked to the pathogenesis of DMD which means its pharmacological control can lead to control of muscular degeneration. The drugs used still need to be refined to make them more effective in the treatment of DMD. I chose this particular article because Duchene Muscular Dystrophy is a debilitating illness that affects a significant proportion of the population. In addition, this article offers a new and promising choice of treatment to a group of individuals who hardly have a standard and effective therapeutic option. This will offer an alternative to those suffering the distressing side effects of corticosteroid therapy, which is the current gold standard in the treatment of DMD. I have learnt that Duchene Muscular Dystrophy results from mutations in the dystrophin gene which is responsible for muscle function. In addition I learnt about the treatment options available to DMD patients including glucocorticoids, gene therapy, limited protein intake and the modulation of autophagy by pharmacologic means (De Palma et al., 2014). Reading the article also brought the side effects of corticosteroid therapy to my attention. These include bone demineralization, obesity and immune suppression which in 25% of Duchene Muscular Dystrophy patients limits the use of corticosteroids as a treatment option (De Palma et al., 2014). The second article is a concise review that highlights the reasons why the current methods used in the treatment of anorexia nervosa fail and outlines the rationale for an alternative approach. The authors point out that the reason for failure can be pinned to a misunderstanding of homeostasis with regard to the brain and eating behaviour (Sodersten et al., 2014). In order to underscore this point, overweight, which is the other extreme of anorexia is examined. The conclusion made is that most medical causes of obesity are reversible. However, the pharmacological options available are ineffective and have undesirable side effects (Sodersten et al., 2014).With regard to being underweight, the authors point out that the general assumption is that a chronic mental illness is responsible for the causation of anorexia nervosa. The interventions targeting mental illness often have no effect and when patients are discharged from standard care a majority relapse after a year. An analysis of the brain and eating behaviour indicated that brain messengers serve to increase foraging habits and decrease eating habits when food is in short supply (Sodersten et al., 2014). Alternatively, when there’s an abundance of cheap food the result is eating without biological constraints. This therefore means that the human homeostatic phenotype is the “maintenance of a stable, healthy, low body weight when the physical price of food is high” (Sodersten et al., 2014). As the price lessens, there’s a passive increase in eating and body weight. Anorexia conforms to the homeostatic mechanism highlighted above. This serves to affirm the fact that the endocrinology of anorexia is a reversible consequence of starvation. The authors point out that in as much as an underlying mental disorder is often thought to contribute to the pathogenesis of anorexia nervosa, the evidence against this assertion is overwhelming (Sodersten et al., 2014). With this in mind, treatment offered should aim to restore normal eating behaviour. This can be achieved by using mealtime visual feedback on a computer screen as was done in a randomised control study by Bergh et al., 2013. The results of the study were promising, with no mortality recorded. The authors assert that pharmacological interventions for weight control are bound to fail in view of the fact that neural networks permit excessive eating when eating is easy but not when effort is required (Sodersten et al., 2014). I chose this article because a significant portion of the teenage population is affected by this disorder, that has for a long time been linked to mental illness. Many of those affected are often teenage girls where image has been implicated as the main problem. I have learnt that the link between anorexia nervosa and mental illness is flimsy at best. This therefore means that the treatment options often instituted in the treatment of this condition often fail leading to increased morbidity. In addition, understanding homeostatic mechanisms involved in anorexia are essential if an effective mechanism of treatment is to be devised. References De Palma, C., Perrotta, C., Pellegrino, P., Clementi, E., and Cervia, D. (2014). Skeletal muscle homeostasis in Duchene muscular dystrophy: modulating autophagy as a promising therapeutic strategy. Frontiers of Neuroscience. Retrieved from: http://journal.frontiersin.org/journal/10.3389/fnagi.2014.00188/full Sodersten, P., Bergh, C., Zandian, M and Ioakimidis, I. (2014). Homeostasis in anorexia nervosa. Frontiers in Neuroscience. Retrieved from: http://journal.frontiersin.org/journal/10.3389/fnins.2014.00234/full Read More