William Sander, Class of 2022
The thought of not being able to recognize family members, not reminisce on past memories, and slowly progress to a state where even simple tasks such as communication, eating, and drinking are rendered nearly impossible, are nightmares that are unfathomable. The grim reality is that Alzheimer’s is currently the sixth leading cause of death in the United States (GlobalData Healthcare). Neurologists, among many other doctors, are working tirelessly to try to understand and cure Alzheimer’s disease, and though it is impossible to pinpoint exactly when this may happen, we can say for certain that we are making strides in the right direction. Thus far, scientists have identified two major neurological conditions specific to Alzheimer’s disease: plaque buildup in the brain composed of a protein called amyloid beta and tangles of a protein known simply as tau within neurons in the brain. These plaques are not only believed to disrupt signals in the brain, causing loss of function, but they are thought to dissolve fluid that is pertinent to brain function (Hardy & Selkoe). Many new research projects have targeted the Amyloid Hypothesis, which states that the largest cause of Alzheimer’s disease is the Amyloid Beta protein, have been aimed at somehow reducing these plaques in the brain.
In 2018, there have been two major promising drug trials which targeted the Amyloid Hypothesis as the backbone of their approach. The first trial where a drug called solanezumab, described as “...a monoclonal antibody-based treatment for Alzheimer's disease” developed by Eli Lilly was anticipated to be a promising step forward in the fight against Alzheimer’s disease (MedicalXPress). In theory, this chemical targets amyloid plaques; however, in phase III of the clinical trials, this drug failed to show any kind of decrease in the detrimental effects of Alzheimer’s disease. This revelation dealt a huge blow to the hope for a cure to Alzheimer’s, but Dr. Lawrence Honig, a researcher involved in the clinical trial, stated, "Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study” (MedicalXPress). Another clinical trial tested another drug called Azeliragon, which is aimed at blocking the formation of plaques in the brain by inhibiting protein attachment to blood cells that are travelling to the brain (GlobalData Healthcare). The main concern behind this drug is that the reasoning and evidence is largely unfounded and lacks efficacy data. While little data has been produced in this clinical trial it does not appear to be successful, as it has already had three pipeline failures, but this is not to say there is no hope for future research and a possible cure for Alzheimer’s Disease.
New research being done at the University of Cambridge and at Lund University in Sweden has demonstrated that the destruction of nerve cells, as seen in Alzheimer’s disease and other forms of dementia, may not be a property of the amyloid beta plaques in the brain, but rather the toxic protein oligomers that are being secreted by the amyloid beta proteins. Professor Sir Christopher Dobson, a researcher in the project, stated that this group now has the capability to find compounds that may combat the toxic oligomers in the brain and could potentially reduce these “clumps” and, thus, reduce the memory loss effects of Alzheimer’s disease (MedicalXPress).
Regardless of the failed trials, which have given scientists valuable information into how to approach curing Alzheimer’s disease, there are a plethora of new clinical studies making their way to trials. Aside from these promising trials, it should be noted that we do not fully understand Alzheimer’s disease yet and that the validity of the Amyloid Hypothesis should be further reviewed, as there is still much debate surrounding the topic. In fact, the most common objection to this hypothesis is that the amount of Amyloid clusters in the brain are not directly attributable to magnitude of memory loss that a person may be experiencing (Hardy & Selkoe). Wherever Alzheimer’s research may take us in the future it is critical to continue to reevaluate the techniques and validity of the hypotheses and methods that scientists and medical professionals use in order to finally find a cure to this detrimental disease.
References
1.) GlobalData Healthcare. “Azeliragon: The Third Alzheimer's Failure of 2018.” Pharmaceutical Technology, 17 Apr. 2018, www.pharmaceutical-technology.com/comment/azeliragon-third-alzheimers-failure-2018.
2.) Hardy, John, and Dennis J. Selkoe. “The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics.” Science, American Association for the Advancement of Science, 19 July 2002, science.sciencemag.org/content/297/5580/353.
3.) Science X. “Alzheimer's Drug Targeting Soluble Amyloid Falls Short in a Large Clinical Trial.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 25 Jan. 2018, medicalxpress.com/news/2018-01-alzheimer-drug-soluble-amyloid-falls.html.
4.) Science X. “Scientists Reveal Ground-Breaking Plan to Target Cause of Alzheimer's Disease.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 24 Sept. 2018, medicalxpress.com/news/2018-09-scientists-reveal-ground-breaking-alzheimer-disease.html.
In 2018, there have been two major promising drug trials which targeted the Amyloid Hypothesis as the backbone of their approach. The first trial where a drug called solanezumab, described as “...a monoclonal antibody-based treatment for Alzheimer's disease” developed by Eli Lilly was anticipated to be a promising step forward in the fight against Alzheimer’s disease (MedicalXPress). In theory, this chemical targets amyloid plaques; however, in phase III of the clinical trials, this drug failed to show any kind of decrease in the detrimental effects of Alzheimer’s disease. This revelation dealt a huge blow to the hope for a cure to Alzheimer’s, but Dr. Lawrence Honig, a researcher involved in the clinical trial, stated, "Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study” (MedicalXPress). Another clinical trial tested another drug called Azeliragon, which is aimed at blocking the formation of plaques in the brain by inhibiting protein attachment to blood cells that are travelling to the brain (GlobalData Healthcare). The main concern behind this drug is that the reasoning and evidence is largely unfounded and lacks efficacy data. While little data has been produced in this clinical trial it does not appear to be successful, as it has already had three pipeline failures, but this is not to say there is no hope for future research and a possible cure for Alzheimer’s Disease.
New research being done at the University of Cambridge and at Lund University in Sweden has demonstrated that the destruction of nerve cells, as seen in Alzheimer’s disease and other forms of dementia, may not be a property of the amyloid beta plaques in the brain, but rather the toxic protein oligomers that are being secreted by the amyloid beta proteins. Professor Sir Christopher Dobson, a researcher in the project, stated that this group now has the capability to find compounds that may combat the toxic oligomers in the brain and could potentially reduce these “clumps” and, thus, reduce the memory loss effects of Alzheimer’s disease (MedicalXPress).
Regardless of the failed trials, which have given scientists valuable information into how to approach curing Alzheimer’s disease, there are a plethora of new clinical studies making their way to trials. Aside from these promising trials, it should be noted that we do not fully understand Alzheimer’s disease yet and that the validity of the Amyloid Hypothesis should be further reviewed, as there is still much debate surrounding the topic. In fact, the most common objection to this hypothesis is that the amount of Amyloid clusters in the brain are not directly attributable to magnitude of memory loss that a person may be experiencing (Hardy & Selkoe). Wherever Alzheimer’s research may take us in the future it is critical to continue to reevaluate the techniques and validity of the hypotheses and methods that scientists and medical professionals use in order to finally find a cure to this detrimental disease.
References
1.) GlobalData Healthcare. “Azeliragon: The Third Alzheimer's Failure of 2018.” Pharmaceutical Technology, 17 Apr. 2018, www.pharmaceutical-technology.com/comment/azeliragon-third-alzheimers-failure-2018.
2.) Hardy, John, and Dennis J. Selkoe. “The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics.” Science, American Association for the Advancement of Science, 19 July 2002, science.sciencemag.org/content/297/5580/353.
3.) Science X. “Alzheimer's Drug Targeting Soluble Amyloid Falls Short in a Large Clinical Trial.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 25 Jan. 2018, medicalxpress.com/news/2018-01-alzheimer-drug-soluble-amyloid-falls.html.
4.) Science X. “Scientists Reveal Ground-Breaking Plan to Target Cause of Alzheimer's Disease.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 24 Sept. 2018, medicalxpress.com/news/2018-09-scientists-reveal-ground-breaking-alzheimer-disease.html.
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