Novel Drug Therapy Immediately Reverses Alzheimers Cognitive Deficits - Term Paper Example

Alzheimer’s disease: Introduction The disease of Alzheimer refers to a particular disorder in human brain. The name of this disease has been derived from a German Physician named Alois Alzheimer. The disease was described for the first time by Dr. Alzheimer in the year of 1906. Since the time this disease got attention for the first time, almost a century has been passed and substantial progress has been made by the scientists in the understanding and treatment of this disease. Today Alzheimer’s is recognized as one of the most fatal brain diseases. In America itself, around 5.3 million people are suffering from this brain disorder. Alzheimer’s severely affected the brain cells and stop them working in normal ways. People who suffer from the disease of Alzheimer loose their memory and experience behavioral disorders. In the United States, Alzheimer’s has emerged as the seventh-leading factor causing the deaths of the people living there. Looking at the severity of this disease it would be quite interesting to look at the various aspects relating to this fatal brain disorder. Hence, the nature of this disease, its symptoms, recent developments in its understandings and treatment will be discussed in this paper. (What is Alzheimers, 2009) A Brief Overview of the disease of Alzheimer’s As the other parts of the human body, brain changes with increase in age. Very often aged people show slowed thinking or problems in remembering things occasionally. These are some normal symptoms of old age. But when a person suffers with serious loss in memory along with major behavioral disorders, then these can not be treated as normal features of ageing, but these are the signs of failing brain cells or the Alzheimer’s disease. An interesting feature about this disease is that the progress rate of it is very slow implying it takes a long time to reach its matured stage. It is mainly characterized by the features like impairment of human memory and eventual decline in the reasoning and planning efficiency and increases in the disturbances in language and perceptions regarding various things. According to many scientists, the increase in the production of a particular protein, commonly known as beta-amyloid, in the human brain causes the disease of Alzheimer by destroying the nerve cells. The probability of having this fatal disease becomes very high after the age of seventy and around fifty percent of people over the age of eighty five might get affected with Alzheimer’s disease. (What is Alzheimers. 2009; Crystal, n.d) Over the years, scientists have conducted to several researches to find out the factors that play major roles in the development of this disease. The increase in age has been found to be the main risk factor for it. With increase in age the probability of having this disease also rises sharply. According to some estimate, if no spectacular advances are made in the treatment of this disease, by 2050 as many as 14 million people will be affected by it. Apart from age, some genetic factors also lead to the development of Alzheimer’s disease. Although most of the people develop this disease mainly after they cross 70 years of their lives, around 2-5 percent of patients develop this disease only after 40 or 50 years. As many as half of these patients who develops the disease at relatively early ages of their lives, have genetic disorders that they inherit. Not only have the cases of early-onset of the disease, but some late-onset of Alzheimer’s disease cases also have been encountered with genetic problems as the main risk factor. Apart from the risk factors of age and genetic mutation, hypertension, diabetes, high cholesterol in blood vessels, coronary artery disease etc can cause this disease or increase the probability of having it. (Crystal, n.d; Brookmeyer et al. 2007) As far as the symptoms of the disease are concerned, the onset of it is mainly found to be quite gradual with slow rate of progress. The problem of gradual loss in memory is considered to be the first stage of Alzheimer’s disease. But very often this symptom of memory loss is initially treated by the family members as a normal feature of ageing. The family members of most of the patients affected by Alzheimer’s disease start to think that something more than normal part of ageing is happening only after memory problems accompanied by various other problems in the thinking process of the patients start to affect their behavior consistently. (Crystal, n.d.) Among the symptoms of the Alzheimer’s disease, the most common one at the very early stage of this disease is short term memory loss, where the affected person fails to remember very recent events. Apart from it, some changes in the personality can also be encountered although at mild level at the early stage of this disease. For example, at the person may become less spontaneous, may develop a tendency of reducing the level of social interactions, etc. With the progress of the disease, some other symptoms emerge. For example, various problems in abstract thinking and in many other intellectual functioning develop. An individual affected by the Alzheimer’s disease may start to face various troubles in his or her daily activities, like problems with calculations while working on some bills, or in understanding perfectly what he or she is reading, or with organizing his or her daily work schedule. Apart from these problems, some other behavioral problems also emerge. For instance, the individual develops the tendency of getting agitated or irritated on small issues, become very quarrelsome etc. The person also loses his or her sense of dressing appropriately. In the more advanced phase of this disease, the patients become very of confused about the current year or month or date, find it quite difficult to recall properly the places where they live or the places which they have visited very recently. Gradually, they loose their ability to engage in any kind normal conversation, become very unpredictable as well as uncooperative in nature. They also suffer from loss in bowel control. In the very final stage of the disease, the affected individuals become totally incapable of taking care of themselves and they eventually move towards the end of their life. Very often death follows from pneumonia or other problems that can occur at the severely deteriorated heath condition. (Crystal, n.d.) Recent developments in the understanding of Alzheimer’s disease Scientists have been trying to enhance the understanding regarding the fatal disease of Alzheimer. In recent times, huge development has taken place in this regard and several missing links have been discovered in the understanding of these diseases. For example, earlier age was considered to be the sole risk factor responsible for the occurrence of the disease. But over time, researchers have found that age is not the only factor responsible for the development of Alzheimer’s conditions. As mentioned in this paper earlier high blood pressure, high cholesterol etc. can increase the likelihood of having the disease by manifolds. Hence researchers suggest that by controlling blood pressure, the cholesterol level etc. the probability of having the disease can be reduced even at very old age. Apart from this, in recent time, European researchers have found a close link in terms of molecule between Alzheimer’s and amyloid plaques’ development. Amyloid plaques is considered to be one of the most important hallmarks of Alzheimer’s disease. (Research provides better understanding of Alzheimers, 2008) An important feature of this disease is that between nerve cells in the human brains, amyloid plaques are formed. Amyloids are actually fragments of protein that are normally produced in the body. These protein fragments are broken down and eventually eliminated in a healthy normal brain. But when the brain is affected by Alzheimer’s disease these protein fragments accumulate and develop hard and insoluble plaques in the brain. A number of years ago, a Belgium research team led by Dr. Bart De Strooper to discovered the procedure through which these protein fragments in the brain develop into the common form of Alzheimer’s disease. They found that an enzyme, γ-secretase, which fragments protein in a specific place, plays very crucial role in the development of plaques. The research team found that on some occasions the process of cutting proteins by the γ-secretase goes in wrong way which in turn causes a kind of by-product that makes the protein fragments sticking together and thus forms plaques. However, till now no clear idea regarding the exact process of the formation of these plaques has been obtained. (Research provides better understanding of Alzheimers, 2008) In the latest study conducted by the EU researchers, attention have been paid on finding out the major causes that help in the increase of an aspartic protease enzyme known as ß-secretase (BACE1). This enzyme has been found to be present in the brains of the patients who have been affected by Alzheimer’s disease. The production of ß-secretase (BACE1) is mainly regulated by miRNAs which are nothing but small pieces of RNA. The research team has looked into the expression profiles of these mi-RNAs to find out probable causes of increase ß-secretase (BACE1). The research has found that the affected individuals with higher level of this protein also had relatively lower level of miR-29a as well as miR-29b-1. Following the findings this research team is of the opinion that some miRNAs may be responsible for increase in ß-secretase and in turn development of the protein plaques in the brains. The researchers also state that there lies immense potential to improve the current structure of diagnostic system adopted by the doctors. According to them if appropriate medicines are prescribed in a timely manner then better responses can be obtained from the patients. (Research provides better understanding of Alzheimers, 2008) In another very important study conducted recently, the researchers are making the claim that they have discovered a very crucial missing link in the understanding of this fatal disease. The researchers have found that it is a kind of cellular protein known as prion which plays a vital role in activating the process through which amyloid-beta secretase causes problems in the normal functioning of the brains of the diseased people. To find out which particular type of amylo-beta is the most likely to cause Alzheimer’s disease, the researchers examined thousands of candidates and found that the amylo-beta attached to the prions is the main culprit. Prion proteins are not normally harmful. They exist in all cells. But on some occasions, these cellular proteins change their shape and may become very harmful and cause damages in the cells. According to this research team since involvement of the proteins can be found at very early stage of the development of the disease, these can be an appropriate target for the development of new treatments for Alzheimer’s disease. (Trombetti, 2009) Recent developments in the treatment of Alzheimer’s disease The current drugs approved for the treatment of Alzheimer’s disease are not very effective in preventing or reversing the disease. They are only able to produce moderate level of effects on the symptoms of the disease on short term basis. Looking at the huge unmet need at the field of the treatment of this disease and given the significant development in the understanding of it, researchers have started to find out more advanced ways of treating this fatal disease. Most of the researchers are now targeting amyloid-beta as researchers have found it to be the main factor causing damages in the cells. (Gervais, 2004; Gura, 2008) Most of the recent strategies for treating Alzheimer’s disease are aimed at preventing the production of amyloid-beta protein in the body, hindering the process of its aggregation to form plaques, reducing its soluble level, as well as disassembling the plaques which have already formed in the brains of the affected persons. Apart from these, a few curative programs of Alzheimer’s disease also aims at lowering the level of phosphorylation of the tau proteins. (Gervais, 2004) Some of the important drugs that have been developed through recent researches on the treatment of the diseases are as follows: Tramiprosate: Most of the recent researches on finding out effective drug for the treatment of Alzheimer’s disease have been aimed at decreasing the level of amyloid-beta formation. Tramiprosate is the first drug which has been tested for its effectiveness in decreasing amyloid-beta. It is basically a glycosaminoglycan mimetic which helps in lowering the aggregations of the amyloid-beta fragments in the brains as well as in promoting their clearance from brain. The second phase of the clinical trial of this drug has demonstrated that it is capable of reducing Aβ42 in the patients’ cerebrospinal fluid. In the third phase of this research with Tramiprosate 1052 individuals having Alzheimer’s disease were selected and they were assigned in a random way to receive the drug in different amounts twice a day. Although the results have shown that no matter what the level of drug intake was, most of the selected patients have been capable of tolerating the treatment. However, the research with Tramiprosate has failed to demonstrate any kind of beneficial effects of the drug on the symptoms of the disease. (Gervais, 2004; Hardy and Selkoe, 2002) Aβ42 vaccines and several Aβ antibodies: In many recent clinical trials application of immunotherapy for preventing the Alzheimer’s disease has become very common. Normally the molecules which help in binding the amyloid-beta peptides can also become quite efficient in drawing this peptide from the brain by some receptor mediator process. Molecules like Heparin, gelsolin and some others are considered to be some effective antibodies that help in reducing the level of accumulation of amyloid beta. (Relkin, 2008) In a clinical trial which has used a first generation vaccine called AN-1792 have shown some positive results in terms of improved response over a one year period in some neuropsychological tests by developing effective antibodies. In another clinical trial a second generation vaccine called ACC-001 is being tested. (Gilman et al. 2005) Recent studies also suggest instead of going for active immunization, some passive immunization measures can also be considered. Under passive immunization anti-amyloid-beta antibodies are regularly administered in the body. This passive immunization process seems to be little more cumbersome from that of the active ones, but they provide higher level of safety and are more efficient in preventing the disease. (Gilman et al. 2005) Anti-TNF-alpha drugs: in a number of recent studies, researchers have found a close link between acute events of inflammation in the brain and the onset and progress of the Alzheimer’s disease. A factor that has been found to cause this inflammation is called TNF-alpha. Several nutrients are capable of lowering the level of TNF-alpha in the brains. But researches have suggested that rduction in the level of TNF-alpha is not sufficient enough for preventing this disease and therefore the ultimate need is to discover such drugs that will be able to reverse the disease’s course. Some anti-TNF drugs like Enbrel® have been approved for the treatment of this disease. (Faloon, 2008) Conclusion Over time Alzheimer’s disease has attracted wide attentions from the medical scientists. Significant development has been made in the understandings and treatment of this fatal disease. But the thing to worry is that no such magnificent outcome has been obtained in preventing or curing this disease. Scientists have developed a number of new drugs to increase efficiency in the treatment process. But currently most of these drugs are at their trial stages. Those drugs which are now being prescribed for treating the disease seem to be not so effective. So there still exists huge scope of research on this disease and scientists are still required to come up with desired results. References: 1. aloon, W. 2008. Novel Drug Therapy Immediately Reverses Alzheimer’s Cognitive Deficits. Available at http://www.lef.org/magazine/mag2008/aug2008_Novel-Drug-Therapy-Immediately-Reverses-Alzheimers-Cognitive-Deficits_01.htm [accessed on 13th July, 2009]. 2. Hardy, J. and Selkoe, D.J. 2002. The amyloid hypothesis of Alzheimers disease: progress and problems on the road to therapeutics. Science, 297:353-356 3. Gervais, F. 2004. GAG mimetics: potential to modify underlying disease process in AD. Neurobiol Aging, 25:S11-12. 4. Relkin, N.R. 2008. Current state of immunotherapy for Alzheimers disease. CNS Spectr,1:39-41. 5. Gilman, S, Koller, M, Black, R.S., Jenkins. L, Griffith. S.G., Fox, N.C., Eisner, L., Kirby, L., Rovira, M.B., Forette, F. and Orgogozo, J.M. 2005. 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