Research Proposal on "Alzheimer's 7 Ways to Save a Brain by Underwood a 2005 Summer"

Research Proposal 6 pages (2229 words) Sources: 5 Style: APA

[EXCERPT] . . . .

ground breaking and innovative instances of research that claim to help patients suffering from Alzheimer's disease. The article begins by claiming that an 85-year-old woman, Elizabeth Harvey, who began suffering from the dementia related to Alzheimer's disease has been given an experimental treatment, which has resulted in a retardation of the progression of the disease. This retardation is marked by the fact that there is no cognitive impairment even two years after the symptoms of Alzheimer's first appeared.

The author summarizes the results of seven studies in single paragraphs. There is also an implicit dig at the Federal Drug Association (FDA), which if often criticized for dragging its feet in certifying novel, innovative and (potentially) risky treatment modalities which could be life saving. The drugs and treatments methods that are described in this article are not necessarily preventive or curative. Indeed, they are more effective for patients who are in the early stages of the disease, and do not retard the progress of the disease in relatively advanced patients. But, as Underwood avers, to increase the quality of life for about five years is to reduce the burdens the ravages of the disease places on the patients and their near and dear ones.

One important point that Underwood tries to make starts out with a note of warning that the number of people suffering from Alzheimer's disease will increase to several millions in a few years. This is in support of the previously mentioned point of the FDA being more aggressive in certifying new medication. One way to do this would be to have compulsory brain scans for patients. Biomarkers would then help identify those that are at high risks for Alzheimer's disease. Since the treatments that the article identifies are more preventive then curative, the patients are likely to delay the onset of the symptoms.

In order to explain the preventive nature of these medications, Underwood uses an analogy provided by a Harvard researcher. The brain is compared to a tub full of water; and the only way to prevent overflowing is to turn off the "spigot" or open the drain. There are two different schools of thought when it comes to Alzheimer's disease. What causes Alzheimer's disease therefore, is either through plaques or neurofibrillary tangles. The treatment methods described in this article have more to do with plaques, and not the tangles.

This article follows the premise that most of the medications target the A (myloid)-beta protein. The first treatment mentioned in mentions the medication Alzhemed.

(Walsh, Tseng, Rydel, Podlisny, & Selkoe, 2000) ADDIN EN.CITE This is the treatment that helped Elizabeth Harvey, by helping her retain her cognitive skills while at the same time delaying the retardation of the progress of the disease. Plaques are caused when the A-Beta proteins clump together. Alzhemed is also known by another name, Tramiprosate. The chemical name for this small molecule is 3-aminopropylsulfonic acid. This medication is taken by mouth. The molecule is very small. It consists of a three carbon chain atom with a sulfonyl group at one end and an amino group at the other end. This medication is known to cross the blood brain barrier before depositing on the Amyloid beta proteins. As has been mentioned previously in the essay, Alzhemed only works in case of mild to moderate symptoms of Alzheimer's disease; it is however, not useful in the later stages of the disease. It isn't FDA approved. While the general theme of this paper is implicitly critical of the FDA, the alzforum.org web resource for Alzheimer's disease (Alzforum, 2009) indicates that A Phase III trial is known to have failed.

The second study is related to immunology and Alzheimer's disease. Our bodies are constantly being bombarded by pathogens and foreign bodies. The immune system is a combination of T-cells, B-cells and White Blood Cells in plasma, which kicks into overdrive to destroy the attacking entity. The immune system is composed of antibodies, which are two tiered, Y-shaped bodies which consist of conserved proteins regions which maintain the shape of the antibody and a variable protein region which is responsible for binding to different antigens (attacking entities). The variability of the protein region is critical. This is because a fixed set of antibodies have to be able to deal with potentially millions of different antigens.

The antibodies also play other roles, those of regulatory enzymes. Within the context of Alzheimer's disease, antibodies also lower the expression of Amyloid Beta proteins. Two researchers at the Weill Cornell Medical College in New York City, an institution that looks upon New York's Jefferson Island concurred that the antibodies that regulated Amyloid beta proteins were at a lower level in Alzheimer's patients. To raise the levels of antibodies, the two researchers, in a clinical trial injected the immunoglobulins directly into the brain of the patients. This treatment was a significant success in the tested patients. It increased the mental acuity of the patients. Amyloid-beta proteins are produced in the Alzheimer's glands in the cortex of the brain.

In a related study, a vaccine AN1792 was also tested, using the same principle of immunoglobulin treatment. (Parker, 2004) But some of the patients developed encephalitis and the study had to be abandoned. (BBC, 2003) The researchers averred that this was because of the auto-immune response to the treatment.

Proteins are incredible entities in the system. They are created by genes through a process of transcription followed by translation. Proteins have functions, most of which have not been identified. For example, when DNA is damaged, it manufactures a protein temporarily so that it interacts with the DNA while it is being repaired. (Feng, Crasto, & Matsumoto, 1998) Enzymes are catalysts responsible for catalyzing biological processes at rates that cannot be replicated in a laboratory setting. Proteins are also responsible for the manufacture of other proteins. This was the crux of the treatment that researchers at Torrey Pines research facilities provided. They sought to block the production of a gamma secretase, which was responsible for the production of the Amyloid-beta protein. Unfortunately, blocking the expression of gamma secretase interfered with the production of other proteins which were responsible for other vital functions in the brain. Additional research at Torrey Pines resulted in the creation of a blocker which specifically interacts with amyloid-beta protein interfering with its expression.

The kind of research that resulted in the identification of a specific blocker of amyloid beta is called QSAR or Quality Structure Activity Relationship. (Richon & Young, 2009) This is a methodology that involves high throughput studies. A large number of molecules are evaluated to see which one will interact with a target. The evaluations involve studying the structure of the molecule and its electronic character to determine which combination is more likely to foster the interaction between the molecule and its target. The number of possible combinations are then reduced and further tested until the right molecule is found. The focused number of targets is even tested experimentally. The Torrey Pines study involved a high throughput system involving more than 80,000 starting compounds.

As has been mentioned previously, some of the studies described briefly by Anne Underwood involve targeting Amyloid-beta proteins. Researchers have also been studying hormones as a treatment against Alzheimer's disease. The finding was accidental. An Alzheimer's patient did not find any deterioration because he took medication called leuprolide (Voyager, 2009)for prostate cancer. This treatment prevents the creation of gonadotropins which are over expressed in patients with Alzheimer's disease.

Dr. John Trojanowski from the University of Pennsylvania is the leader of one of the studies that pursues neurofibrillary tangles and not amyloid-beta proteins.(Uryu et al., 2007) The drug of interest in this case is Taxol. Originally used as a cancer drug, it has shown promise in the treatment of Alzheimer's disease. No human testing has taken place. Most of the testing is taken place in mice. Trojanowski and his research group hope that Taxol can strengthen microtubles, which are susceptible to neurofibrillary tangles.

One of the advantages of testing the use of Taxol for Alzheimer's disease is that all the testing on humans has already been done during the trials for the use of Taxol in the treatment of cancer. Therefore, the researchers are confident that testing of Taxol can proceed to human testing without going through intermediate phase clinical trials. Taxol's scientific name is Paclitaxel. (ChemoCare, 2005) It is a chemotherapy drug. It is a broad spectrum drug in the treatment of various cancers, including breast, ovarian, lung, bladder, prostate, melanoma and esophageal cancers. Taxol as a chemotherapy drug has several side effects. The patient undergoing chemotherapy is not likely to suffer from all the side effects. The side effects go away as son as the chemotherapy treatment runs its course.

Gene therapy is an innovative style treatment that came on the heels of advanced study in DNA. Several discoveries showed that disease were caused because of defective genes. The notion of gene therapy came about when researchers felt that if they… READ MORE

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