Vincent Li, Class of 2022
Alzheimer’s disease, originally named after Dr. Alois Alzheimer for his identification of the illness in 1906, ranks among one of the highest causes of death among the elderly, just behind cancer and cardiac diseases (3). Alzheimer’s is the most prevalent form of dementia: defined by the National Institute on Aging as “the loss of cognitive functioning… and behavioral activities” (2). Though the disease claims so many lives and reduces the quality of living for the geriatric, it has remained incurable in the sense that currently available treatments and therapies only mitigate its effects and slow the rate at which the brain decays.
However, German researchers from Heinrich Heine University Düsseldorf and Forschungszentrum Jülich recently created a new drug named PRI-002 that may eliminate “toxic beta-amyloid oligomers,” considering the drug has been found to “reduce… symptoms in older mice” that have been “genetically engineered to develop an Alzheimer’s-like disease” (5). To break this down: Alzheimer’s symptoms are caused by the deposition of the aforementioned beta-amyloid plaques (fragments of proteins clumped together), which prevent neurons from properly communicating, and tau protein tangles, which orient themselves to disrupt transportation of waste and nutrients (1). As a result, brain cells become isolated and unable to interact with one another, gradually dying out while the brain shrinks due to a lack of sustenance. It is this cell death that causes the loss of a patient’s mental faculties until bodily functions ultimately terminate.
Due to the variation in the supposed causes of Alzheimer’s—genetics, lifestyle, and environment—scientists have focused their research onto these two proteins, as having an all-encompassing method to eliminate both the plaque deposits and protein tangles would preserve mental ability and prevent death. Rather than just slowing the inevitable, research focusing on beta-amyloids may be conducive to a drug that would prevent the amyloid clumps from forming and breaking neural connections. If successful, one of the major causes of Alzheimer’s would become a non-issue.
And while news of groundbreaking discoveries in nonhuman models seems promising, potential drugs fail to reach clinical trials, in which testing begins on human volunteers rather than model organisms. Even still, there is the likelihood of the drug having little to no effect on humans due to the innate differences in the biological systems between human and animal models. Or worse, the drug may have severe negative consequences that were dormant when tested on mice or rabbits, and so forth. So what exactly makes PRI-002 any different from the plethora of drugs that never make it to clinical trials, or those that do but ultimately fail?
Given its effectiveness on mice trials, this particular drug has already overcome the gauntlet of reaching the first phase of clinical trials, in which “healthy volunteers took daily dosages of PRI-002 for 4 weeks”(5). As no adverse effects appeared throughout the monitoring of these individuals, PRI-002 will be moving onto the second phase of clinical trials: testing the effectiveness of the drug in human patients afflicted with Alzheimer’s. According to Professor Dr. Dieter Willbold, “director of the Structural Biochemistry Institute at Forschungszentrum Jülich and the Institute of Physical Biology at Heinrich Heine University Düsseldorf,” the research team will be processing the next stage with “Priavoid, a private company that they and others from both researcher centers set up in 2017 to develop drugs to treat severe neurological conditions” (5).
However, the process from trial period to clinical implementation is still far from completion. In order to pass the second phase, the drug will need to prove its efficacy in patients with the actual disease. Whether or not the same effect of eliminating toxic amyloid deposits will translate from mice to humans is the major question. To do so, experiments in which a control group (given a placebo or otherwise standard therapy) and an experimental group (given PRI-002) will be analyzed to determine whether the drug has any benefits over current traditional treatments (4). In many cases, blind experiments will be run, in which the researchers and the patients will not be told which drugs were given to whom. This process is to discourage any potential biases that may skew the data in support of the drug. The blind trials will involve hundreds of patients and likely take place over a period of months to even years (4).
Assuming PRI-002 passes phase two, the drug must then undergo phases three and four, which will prove even more arduous. Phase three will be an upscaled version of phase two, in which the scope of thousands of patients will be tested to obtain an even more comprehensive understanding of the drug, its effects, and any adverse effects that may appear in certain individuals with predisposed conditions or other medication usage (4). It is likely to take several years to pass this phase as well (4). Phase four’s purpose is to compare the drug’s long-term effects, cost-efficiency, and impact on quality of life, with other medications already on the market (4).
According to CenterWatch, “about 70% of experimental drugs pass [Phase I],” “about one-third… complete both Phase I and Phase II,” and “70% to 90% of drugs that enter Phase III studies… complete this phase” (4). From these general statistics, it becomes clear that one of the larger hurdles PRI-002 must face is Phase II, and that while the drug has already passed a number of stages, there are still more to come.
Though its future prospect, PRI-002 is a step in the right direction as researchers begin targeting the root causes of Alzheimer’s disease. Ideally, it will only be a matter of time before other drugs, perhaps even based off of PRI-002, pass the gamut of drug testing, reach consumers, and maybe even make Alzheimer’s a manageable disease on the same level of asthma or diabetes.
References
1. Alzheimer's disease. (2018, December 08). Retrieved May 26, 2019, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447
2. Alzheimer's Disease Fact Sheet. (n.d.). Retrieved May 26, 2019, from https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet
3. Number of Alzheimer's deaths found to be underreported. (n.d.). Retrieved May 26, 2019, from https://www.nia.nih.gov/news/number-alzheimers-deaths-found-be-underreported
4. Overview of Clinical Trials. (n.d.). Retrieved May 26, 2019, from https://www.centerwatch.com/clinical-trials/overview.aspx/
5. PhD, C. P. (2019, May 15). Novel Alzheimer's drug passes first phase of human testing. Retrieved May 26, 2019, from https://www.medicalnewstoday.com/articles/325183.php
However, German researchers from Heinrich Heine University Düsseldorf and Forschungszentrum Jülich recently created a new drug named PRI-002 that may eliminate “toxic beta-amyloid oligomers,” considering the drug has been found to “reduce… symptoms in older mice” that have been “genetically engineered to develop an Alzheimer’s-like disease” (5). To break this down: Alzheimer’s symptoms are caused by the deposition of the aforementioned beta-amyloid plaques (fragments of proteins clumped together), which prevent neurons from properly communicating, and tau protein tangles, which orient themselves to disrupt transportation of waste and nutrients (1). As a result, brain cells become isolated and unable to interact with one another, gradually dying out while the brain shrinks due to a lack of sustenance. It is this cell death that causes the loss of a patient’s mental faculties until bodily functions ultimately terminate.
Due to the variation in the supposed causes of Alzheimer’s—genetics, lifestyle, and environment—scientists have focused their research onto these two proteins, as having an all-encompassing method to eliminate both the plaque deposits and protein tangles would preserve mental ability and prevent death. Rather than just slowing the inevitable, research focusing on beta-amyloids may be conducive to a drug that would prevent the amyloid clumps from forming and breaking neural connections. If successful, one of the major causes of Alzheimer’s would become a non-issue.
And while news of groundbreaking discoveries in nonhuman models seems promising, potential drugs fail to reach clinical trials, in which testing begins on human volunteers rather than model organisms. Even still, there is the likelihood of the drug having little to no effect on humans due to the innate differences in the biological systems between human and animal models. Or worse, the drug may have severe negative consequences that were dormant when tested on mice or rabbits, and so forth. So what exactly makes PRI-002 any different from the plethora of drugs that never make it to clinical trials, or those that do but ultimately fail?
Given its effectiveness on mice trials, this particular drug has already overcome the gauntlet of reaching the first phase of clinical trials, in which “healthy volunteers took daily dosages of PRI-002 for 4 weeks”(5). As no adverse effects appeared throughout the monitoring of these individuals, PRI-002 will be moving onto the second phase of clinical trials: testing the effectiveness of the drug in human patients afflicted with Alzheimer’s. According to Professor Dr. Dieter Willbold, “director of the Structural Biochemistry Institute at Forschungszentrum Jülich and the Institute of Physical Biology at Heinrich Heine University Düsseldorf,” the research team will be processing the next stage with “Priavoid, a private company that they and others from both researcher centers set up in 2017 to develop drugs to treat severe neurological conditions” (5).
However, the process from trial period to clinical implementation is still far from completion. In order to pass the second phase, the drug will need to prove its efficacy in patients with the actual disease. Whether or not the same effect of eliminating toxic amyloid deposits will translate from mice to humans is the major question. To do so, experiments in which a control group (given a placebo or otherwise standard therapy) and an experimental group (given PRI-002) will be analyzed to determine whether the drug has any benefits over current traditional treatments (4). In many cases, blind experiments will be run, in which the researchers and the patients will not be told which drugs were given to whom. This process is to discourage any potential biases that may skew the data in support of the drug. The blind trials will involve hundreds of patients and likely take place over a period of months to even years (4).
Assuming PRI-002 passes phase two, the drug must then undergo phases three and four, which will prove even more arduous. Phase three will be an upscaled version of phase two, in which the scope of thousands of patients will be tested to obtain an even more comprehensive understanding of the drug, its effects, and any adverse effects that may appear in certain individuals with predisposed conditions or other medication usage (4). It is likely to take several years to pass this phase as well (4). Phase four’s purpose is to compare the drug’s long-term effects, cost-efficiency, and impact on quality of life, with other medications already on the market (4).
According to CenterWatch, “about 70% of experimental drugs pass [Phase I],” “about one-third… complete both Phase I and Phase II,” and “70% to 90% of drugs that enter Phase III studies… complete this phase” (4). From these general statistics, it becomes clear that one of the larger hurdles PRI-002 must face is Phase II, and that while the drug has already passed a number of stages, there are still more to come.
Though its future prospect, PRI-002 is a step in the right direction as researchers begin targeting the root causes of Alzheimer’s disease. Ideally, it will only be a matter of time before other drugs, perhaps even based off of PRI-002, pass the gamut of drug testing, reach consumers, and maybe even make Alzheimer’s a manageable disease on the same level of asthma or diabetes.
References
1. Alzheimer's disease. (2018, December 08). Retrieved May 26, 2019, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447
2. Alzheimer's Disease Fact Sheet. (n.d.). Retrieved May 26, 2019, from https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet
3. Number of Alzheimer's deaths found to be underreported. (n.d.). Retrieved May 26, 2019, from https://www.nia.nih.gov/news/number-alzheimers-deaths-found-be-underreported
4. Overview of Clinical Trials. (n.d.). Retrieved May 26, 2019, from https://www.centerwatch.com/clinical-trials/overview.aspx/
5. PhD, C. P. (2019, May 15). Novel Alzheimer's drug passes first phase of human testing. Retrieved May 26, 2019, from https://www.medicalnewstoday.com/articles/325183.php
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