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October 6, 2021Alzheimer's | A review
Neurodegenerative diseases pose a major threat to human health. These age-dependent disorders are becoming increasingly prevalent, in part because the elderly population has increased in recent years. The term neurodegenerative is generic, but it covers, according to DG Health and Food Safety, a body of the European Commission, more than 600 conditions that affect the neurons of the human brain. Examples of neurodegenerative diseases are Alzheimer's disease, which is estimated to account for 60 to 70 percent of dementia cases worldwide, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis - ALS, frontotemporal dementia and spinocerebellar ataxias. These diseases are diverse in their pathophysiology - some cause memory problems and cognitive problems and others affect a person's ability to move, speak and breathe, among other complications.
Alzheimer's disease is the most common subtype of dementia. A dementia designates a syndrome, that is, a set of signs and symptoms that reflect the loss of cognitive functions. Several diseases can manifest as a dementia syndrome, the most frequent being Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disease characterized by progressive loss of cognitive functions, which is associated with behavioral changes and functional disability.
The most frequent cognitive symptoms of Alzheimer's disease include memory loss, difficulty planning or solving problems, difficulty understanding visual images and spatial relationships, and difficulty performing familiar tasks.
In the early stages, symptoms of Alzheimer's Disease can be very subtle. However, they often start with memory lapses and difficulty finding the right words for everyday objects.
These symptoms get worse as the brain cells die and the communication between them is altered. Other characteristic symptoms also include persistent and frequent memory difficulties, especially from recent events; present a vague speech during conversations; losing enthusiasm in carrying out activities that were previously appreciated; take more time to perform routine activities; forgetting about familiar people or places; inability to understand questions and instructions; deterioration of social skills and emotional unpredictability.
The name of this disease comes from Alois Alzheimer, a German physician who in 1907 first described the disease.
As the brain cells undergo a reduction in size and number, neurofibrillary tresses form inside them and senile plaques in the outer space between them. This situation makes communication within the brain impossible and damages existing connections between brain cells. These eventually die and this translates into an inability to remember the information. In this way, as Alzheimer's Disease affects the various brain areas, certain functions or capacities are lost.
Alzheimer's is not clearly genetic in character
Medicine does not yet know the cause of Alzheimer's, although the process of brain cell loss is known. What is known is that there is a strong relationship with age, that is, the older you are, the greater the chance of developing the disease. Alzheimer's is not clearly genetic in character, with direct transmission from generation to generation. What is estimated is that there is transmission of the predisposition to develop it, which, together with environmental factors, may or may not trigger it. The first signs are memory loss and the individual's altered behavior. It is not just any memory loss that we should be aware of, but one that repeats itself and begins to compromise the person's daily life, interfering with the functioning of personal activities. Studies that have been developed to determine the composition, secondary metabolites and pharmacological analysis currently play a very important role in the development of drugs for use in this disease. In this context, cannabis appears as a potential therapeutic agent due to the various compounds (cannabinoids and other plant components) that it has, and the neuroprotective characteristics they present for neurodegenerative diseases.
Neurodegenerative diseases are chronic, irreversible and progressive changes characterized by the loss of neurons in the central nervous system (CNS) whose cure is still far away. Cannabis appears as a possible therapeutic weapon since current pharmacological therapy has not had the desired repercussions. The issue is related to the complex mechanisms of pathologies that can be reversed and/or delay development through the plant's compounds, in an attempt to achieve a therapeutic.
Although neurodegenerative diseases are more prevalent in the elderly due to the risk factor of age, sometimes neurons degenerate or die faster than normal than supposed. Some common mechanisms implicit in the progressive nature of neurodegenerative diseases were elucidated: misfolding and protein aggregation, excitotoxicity, mitochondrial dysfunction, oxidative stress and inflammation, even though the etiopathogenesis of these diseases is different.
Today, more than 46 million people live with dementia, and by 2050 that number will have increased to 131.5 million. In just three years, the global economic cost of dementia will reach $1 trillion. In Portugal, 6% of the population suffers from Alzheimer's. As, unfortunately, there is still no satisfactory medical solution for cure or treatment, the impact at the human level is high.
Neurodegenerative diseases, to date, have no cure. Current therapies focus on treating symptoms and trying to delay disease progression. It has been shown that endocannabinoid signaling is altered in many of these diseases, so it is believed that modulation of the endocannabinoid system could be a useful alternative in the treatment of neurodegeneration.
Certain cannabinoids have been shown to limit the action of several cytotoxic stimuli imposed by neurodegeneration: excitotoxicity, mitochondrial dysfunction, oxidative stress and inflammation. Such properties are attractive for the development of new strategies to treat neurodegenerative conditions of diverse etiology. One of the most important characteristics of cannabinoids as potential neuroprotectors is due to their multiple functions, thus broadening their spectrum of activity. This aspect is particularly important in neurodegenerative diseases, since the decline in neuronal function is probably due to the involvement of the different pathological processes mentioned above, which seem to be modulated by the endocannabinoid signaling system.
New therapeutic approaches to treat neurodegenerative conditions
The wide spectrum of activity can be used to develop new therapeutic approaches to treat neurodegenerative conditions. One of the focuses of treatment is the development of ligands to CB2 receptors, as this receptor triggers anti-inflammatory activities and promotes neurogenesis, in addition to being devoid of psychoactive side effects. The advantage of cannabinoids in neuroprotection is their broad-spectrum profile determined by their activity at multiple molecular sites, not only within the endocannabinoid system, but also outside it. Over the years, studies have been carried out with natural and/or synthetic cannabinoids in order to understand how they can act in Alzheimer's disease. Recent studies have shown that the phytocannabinoid, THC, has the ability to competitively inhibit the enzyme acetylcholinesterase (AChE), thereby increasing acetylcholine (ACh) levels. Also, two studies in 2014 show that in small doses of THC, it is able to decrease or delay Ab production, thus preventing the aggregation of Aβ peptides, which could hinder plaque formation. In 2016, results of a study were published that showed that cannabinoids both affect the accumulation of Aβ and interfere with inflammation in nerve cells. The substance THC has been used to improve the symptomatology of side effects triggered by medication for Alzheimer's disease, including nausea, vomiting, diarrhea and weight loss.In other studies, CBD, a non-psychoactive phytocannabinoid, has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. It has several characteristics that could be exploited for the treatment of the disease, including the prevention of excitotoxicity, the reduction of pro-inflammatory mediators, the ability to eliminate reactive oxygen species (ROS) and even reduce lipid oxidation. Therefore, it is being investigated as a possible therapeutic option for Alzheimer's disease. Studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response, as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in rodent models with this disease. Studies in AβPP/PS1 transgenic mice, using 39 combinations of CBD and THC, have shown that CBD can counteract the psychoactive effects associated with THC and possibly improve the therapeutic benefits of any other phytocannabinoid used in monotherapy, and also allow for prevention of memory and reduction of deficits caused by the disease. The in vivo therapeutic potential of CBD in Alzheimer's disease has not been deeply documented, however, there are a number of studies that have reported the effects of CBD in pharmacological models of this disease.
In addition to treatment using cannabinoids and other components of the Cannabis sativa plant, current treatments for Alzheimer's disease aim to neutralize the disease by intervening at specific points in its progression. Scientists are now taking important steps toward ways to prevent, treat and perhaps cure Alzheimer's using antibodies specific to amyloid proteins in the brain.
Antibodies are proteins produced by the body's immune system - they destroy harmful substances like bacteria, toxins, cancer cells and SARS-CoV-2, the virus that causes COVID-19. It is also possible to produce antibodies synthetically, known as monoclonal antibodies.
While studies continue at an astonishing pace for ways to prevent, treat or even cure COVID-19, researchers are finding that synthetic therapy for dementia and Alzheimer's disease also holds promise. Some of the major clinical trials for these new therapies, known as anti-amyloid monoclonal antibodies, are being conducted and show promise.
CB2 plays a significant role in the modulation of inflammatory cascades
Recent studies suggest that unregulated inflammatory cascades may be involved in the origin and development of Alzheimer's disease. Furthermore, there are conclusive studies suggesting that CB2 (receptor of the endocannabinoid system) plays a significant role in the modulation of inflammatory cascades. According to this literature, it has been hypothesized that increased CB2 expression accelerates the progression of Alzheimer's disease. That said, blockade of CB2 with mAbs (monoclonal antibodies), never before developed, should lead to a decrease in Alzheimer's disease markers and glial markers, better physiological responses of hippocampal neurons, improved cognitive and behavioral performance and possible changes in the expression of Aβ (beta amyloid). In addition, Alzheimer's disease is known to be caused by oxidation and consequent inflammatory responses (mediated by the tau protein). Consequently, Aβ (beta amyloid plaque deposition) is merely correlated with the disease, not causally related. As such, the increase in tau protein leads to oxidation and inflammation via iNOS and IL-1b (phosphorylation of tau).The company Piauhy Labs aims to create CB2 mAbs (mAbs are monoclonal antibodies), for the treatment of Alzheimer's disease via the complete DNA expression receptor (deoxyribonucleic acid), under the CMV promoter (cytomegalovirus). Additionally, Piauhy Labs also intends to carry out other experiments based on the following experimental design: mAb against tau (control), mAb + CBD (experimental group); mAb against IL-1b (control), mAb + CBD (experimental); mAb against tau (control), mAb + THC (experimental); mAb against IL-1b (control), mAb + THC (experimental).
References
Budd, H. S.; O'Gorman, J.; Chiao, P. et al. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. The Journal of Prevention of Alzheimer's Disease, 4(4):255-263, 2017.
Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells – Salk Institute for Biological Studies. Published 2016.
Currais, A.; Quehenberger, O.; Armando, A. M.; Daugherty, D.; Maher, P. and Schubert, D. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. npj Aging and Mechanisms of Disease (2016).
Fassler, M.; Rappaport, M. S.; Cuño, C. B. and George, J. Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models. Journal of Neuroinflammation, 18:19, 2021.
Gowran, A.; Noonan, J. and Campbell, V. A. The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. CNS Neurosci. Ther. 17, 6, 637–644, 2011.
Heemels, M. T. Neurodegenerative diseases. Nature 539, 179, 2016.
Karelina, T.; Lerner, S.; Stepanov, A.; Meerson, M. and Demin, O. Monoclonal antibody therapy efficacy can be boosted by combinations with other treatments: Predictions using an integrated Alzheimer’s Disease Platform. CPT: Pharmacometrics & Systems Pharmacology, 10, 8, 2021.
Nishibori, M.; Mori, S. and Takahashi, H. K. Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases. Journal of Pharmacological Sciences, 140, 1, 94-101, 2019.
Sauer, A. The Effects of Medical Marijuana on Alzheimer’s Treatment. Published 2016. Disponível na Internet: http://www.alzheimers.net/6-15-15-effects-of-medical-marijuana-on-alzheimers/. Xing, H., Y.; Li, B.; Peng, D.; Wang, C. Y.; Wang, G. Y.; Li, P. et al. A novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer’s disease. PLoS ONE 12(6), 2017.
Watt, G.: Karl, T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front. Pharmacol. 8 (FEB):1–7, 2017.
The Use of Monoclonal Antibodies in Treatment of Alzheimer Disease Hemen Moradi-Sardareh1, Maryam Moradi2, Elham Bordbar3, Mohammadreza Malekpour4, Sara Bagheri5, Nasrin Nakhodazadeh6, Shahin Rahbar7, Javad Farhadian Asgarabadi8, Meysam Ebrahimi Far9
Budd, H. S.; O'Gorman, J.; Chiao, P. et al. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. The Journal of Prevention of Alzheimer's Disease, 4(4):255-263, 2017.
Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells – Salk Institute for Biological Studies. Published 2016.
Currais, A.; Quehenberger, O.; Armando, A. M.; Daugherty, D.; Maher, P. and Schubert, D. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. npj Aging and Mechanisms of Disease (2016).
Fassler, M.; Rappaport, M. S.; Cuño, C. B. and George, J. Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models. Journal of Neuroinflammation, 18:19, 2021.
Gowran, A.; Noonan, J. and Campbell, V. A. The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. CNS Neurosci. Ther. 17, 6, 637–644, 2011.
Heemels, M. T. Neurodegenerative diseases. Nature 539, 179, 2016.
Karelina, T.; Lerner, S.; Stepanov, A.; Meerson, M. and Demin, O. Monoclonal antibody therapy efficacy can be boosted by combinations with other treatments: Predictions using an integrated Alzheimer’s Disease Platform. CPT: Pharmacometrics & Systems Pharmacology, 10, 8, 2021.
Nishibori, M.; Mori, S. and Takahashi, H. K. Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases. Journal of Pharmacological Sciences, 140, 1, 94-101, 2019.
Sauer, A. The Effects of Medical Marijuana on Alzheimer’s Treatment. Published 2016. Disponível na Internet: http://www.alzheimers.net/6-15-15-effects-of-medical-marijuana-on-alzheimers/. Xing, H., Y.; Li, B.; Peng, D.; Wang, C. Y.; Wang, G. Y.; Li, P. et al. A novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer’s disease. PLoS ONE 12(6), 2017.
Watt, G.: Karl, T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front. Pharmacol. 8 (FEB):1–7, 2017.
The Use of Monoclonal Antibodies in Treatment of Alzheimer Disease Hemen Moradi-Sardareh1, Maryam Moradi2, Elham Bordbar3, Mohammadreza Malekpour4, Sara Bagheri5, Nasrin Nakhodazadeh6, Shahin Rahbar7, Javad Farhadian Asgarabadi8, Meysam Ebrahimi Far9
Alzheimer's - a review
Neurodegenerative diseases pose a major threat to human health. These age-dependent disorders are becoming increasingly prevalent, in part because the elderly population has increased in recent years. The term neurodegenerative is generic, but it covers, according to DG Health and Food Safety, a body of the European Commission, more than 600 conditions that affect the neurons of the human brain. Examples of neurodegenerative diseases are Alzheimer's disease, which is estimated to account for 60 to 70 percent of dementia cases worldwide, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis - ALS, frontotemporal dementia and spinocerebellar ataxias. These diseases are diverse in their pathophysiology - some cause memory problems and cognitive problems and others affect a person's ability to move, speak and breathe, among other complications.
Alzheimer's disease is the most common subtype of dementia. A dementia designates a syndrome, that is, a set of signs and symptoms that reflect the loss of cognitive functions. Several diseases can manifest as a dementia syndrome, the most frequent being Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disease characterized by progressive loss of cognitive functions, which is associated with behavioral changes and functional disability.
The most frequent cognitive symptoms of Alzheimer's disease include memory loss, difficulty planning or solving problems, difficulty understanding visual images and spatial relationships, and difficulty performing familiar tasks.
In the early stages, symptoms of Alzheimer's Disease can be very subtle. However, they often start with memory lapses and difficulty finding the right words for everyday objects.
These symptoms get worse as the brain cells die and the communication between them is altered. Other characteristic symptoms also include persistent and frequent memory difficulties, especially from recent events; present a vague speech during conversations; losing enthusiasm in carrying out activities that were previously appreciated; take more time to perform routine activities; forgetting about familiar people or places; inability to understand questions and instructions; deterioration of social skills and emotional unpredictability.
The name of this disease comes from Alois Alzheimer, a German physician who in 1907 first described the disease.
As the brain cells undergo a reduction in size and number, neurofibrillary tresses form inside them and senile plaques in the outer space between them. This situation makes communication within the brain impossible and damages existing connections between brain cells. These eventually die and this translates into an inability to remember the information. In this way, as Alzheimer's Disease affects the various brain areas, certain functions or capacities are lost.
Alzheimer's is not clearly genetic in character
Medicine does not yet know the cause of Alzheimer's, although the process of brain cell loss is known. What is known is that there is a strong relationship with age, that is, the older you are, the greater the chance of developing the disease. Alzheimer's is not clearly genetic in character, with direct transmission from generation to generation. What is estimated is that there is transmission of the predisposition to develop it, which, together with environmental factors, may or may not trigger it. The first signs are memory loss and the individual's altered behavior. It is not just any memory loss that we should be aware of, but one that repeats itself and begins to compromise the person's daily life, interfering with the functioning of personal activities. Studies that have been developed to determine the composition, secondary metabolites and pharmacological analysis currently play a very important role in the development of drugs for use in this disease. In this context, cannabis appears as a potential therapeutic agent due to the various compounds (cannabinoids and other plant components) that it has, and the neuroprotective characteristics they present for neurodegenerative diseases.
Neurodegenerative diseases are chronic, irreversible and progressive changes characterized by the loss of neurons in the central nervous system (CNS) whose cure is still far away. Cannabis appears as a possible therapeutic weapon since current pharmacological therapy has not had the desired repercussions. The issue is related to the complex mechanisms of pathologies that can be reversed and/or delay development through the plant's compounds, in an attempt to achieve a therapeutic.
Although neurodegenerative diseases are more prevalent in the elderly due to the risk factor of age, sometimes neurons degenerate or die faster than normal than supposed. Some common mechanisms implicit in the progressive nature of neurodegenerative diseases were elucidated: misfolding and protein aggregation, excitotoxicity, mitochondrial dysfunction, oxidative stress and inflammation, even though the etiopathogenesis of these diseases is different.
Today, more than 46 million people live with dementia, and by 2050 that number will have increased to 131.5 million. In just three years, the global economic cost of dementia will reach $1 trillion. In Portugal, 6% of the population suffers from Alzheimer's. As, unfortunately, there is still no satisfactory medical solution for cure or treatment, the impact at the human level is high.
Neurodegenerative diseases, to date, have no cure. Current therapies focus on treating symptoms and trying to delay disease progression. It has been shown that endocannabinoid signaling is altered in many of these diseases, so it is believed that modulation of the endocannabinoid system could be a useful alternative in the treatment of neurodegeneration.
Certain cannabinoids have been shown to limit the action of several cytotoxic stimuli imposed by neurodegeneration: excitotoxicity, mitochondrial dysfunction, oxidative stress and inflammation. Such properties are attractive for the development of new strategies to treat neurodegenerative conditions of diverse etiology. One of the most important characteristics of cannabinoids as potential neuroprotectors is due to their multiple functions, thus broadening their spectrum of activity. This aspect is particularly important in neurodegenerative diseases, since the decline in neuronal function is probably due to the involvement of the different pathological processes mentioned above, which seem to be modulated by the endocannabinoid signaling system.
New therapeutic approaches to treat neurodegenerative conditions
The wide spectrum of activity can be used to develop new therapeutic approaches to treat neurodegenerative conditions. One of the focuses of treatment is the development of ligands to CB2 receptors, as this receptor triggers anti-inflammatory activities and promotes neurogenesis, in addition to being devoid of psychoactive side effects. The advantage of cannabinoids in neuroprotection is their broad-spectrum profile determined by their activity at multiple molecular sites, not only within the endocannabinoid system, but also outside it. Over the years, studies have been carried out with natural and/or synthetic cannabinoids in order to understand how they can act in Alzheimer's disease. Recent studies have shown that the phytocannabinoid, THC, has the ability to competitively inhibit the enzyme acetylcholinesterase (AChE), thereby increasing acetylcholine (ACh) levels. Also, two studies in 2014 show that in small doses of THC, it is able to decrease or delay Ab production, thus preventing the aggregation of Aβ peptides, which could hinder plaque formation. In 2016, results of a study were published that showed that cannabinoids both affect the accumulation of Aβ and interfere with inflammation in nerve cells. The substance THC has been used to improve the symptomatology of side effects triggered by medication for Alzheimer's disease, including nausea, vomiting, diarrhea and weight loss.In other studies, CBD, a non-psychoactive phytocannabinoid, has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. It has several characteristics that could be exploited for the treatment of the disease, including the prevention of excitotoxicity, the reduction of pro-inflammatory mediators, the ability to eliminate reactive oxygen species (ROS) and even reduce lipid oxidation. Therefore, it is being investigated as a possible therapeutic option for Alzheimer's disease. Studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response, as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in rodent models with this disease. Studies in AβPP/PS1 transgenic mice, using 39 combinations of CBD and THC, have shown that CBD can counteract the psychoactive effects associated with THC and possibly improve the therapeutic benefits of any other phytocannabinoid used in monotherapy, and also allow for prevention of memory and reduction of deficits caused by the disease. The in vivo therapeutic potential of CBD in Alzheimer's disease has not been deeply documented, however, there are a number of studies that have reported the effects of CBD in pharmacological models of this disease.
In addition to treatment using cannabinoids and other components of the Cannabis sativa plant, current treatments for Alzheimer's disease aim to neutralize the disease by intervening at specific points in its progression. Scientists are now taking important steps toward ways to prevent, treat and perhaps cure Alzheimer's using antibodies specific to amyloid proteins in the brain.
Antibodies are proteins produced by the body's immune system - they destroy harmful substances like bacteria, toxins, cancer cells and SARS-CoV-2, the virus that causes COVID-19. It is also possible to produce antibodies synthetically, known as monoclonal antibodies.
While studies continue at an astonishing pace for ways to prevent, treat or even cure COVID-19, researchers are finding that synthetic therapy for dementia and Alzheimer's disease also holds promise. Some of the major clinical trials for these new therapies, known as anti-amyloid monoclonal antibodies, are being conducted and show promise.
CB2 plays a significant role in the modulation of inflammatory cascades
Recent studies suggest that unregulated inflammatory cascades may be involved in the origin and development of Alzheimer's disease. Furthermore, there are conclusive studies suggesting that CB2 (receptor of the endocannabinoid system) plays a significant role in the modulation of inflammatory cascades. According to this literature, it has been hypothesized that increased CB2 expression accelerates the progression of Alzheimer's disease. That said, blockade of CB2 with mAbs (monoclonal antibodies), never before developed, should lead to a decrease in Alzheimer's disease markers and glial markers, better physiological responses of hippocampal neurons, improved cognitive and behavioral performance and possible changes in the expression of Aβ (beta amyloid). In addition, Alzheimer's disease is known to be caused by oxidation and consequent inflammatory responses (mediated by the tau protein). Consequently, Aβ (beta amyloid plaque deposition) is merely correlated with the disease, not causally related. As such, the increase in tau protein leads to oxidation and inflammation via iNOS and IL-1b (phosphorylation of tau).The company Piauhy Labs aims to create CB2 mAbs (mAbs are monoclonal antibodies), for the treatment of Alzheimer's disease via the complete DNA expression receptor (deoxyribonucleic acid), under the CMV promoter (cytomegalovirus). Additionally, Piauhy Labs also intends to carry out other experiments based on the following experimental design: mAb against tau (control), mAb + CBD (experimental group); mAb against IL-1b (control), mAb + CBD (experimental); mAb against tau (control), mAb + THC (experimental); mAb against IL-1b (control), mAb + THC (experimental).
References
Budd, H. S.; O'Gorman, J.; Chiao, P. et al. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. The Journal of Prevention of Alzheimer's Disease, 4(4):255-263, 2017.
Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells – Salk Institute for Biological Studies. Published 2016.
Currais, A.; Quehenberger, O.; Armando, A. M.; Daugherty, D.; Maher, P. and Schubert, D. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. npj Aging and Mechanisms of Disease (2016).
Fassler, M.; Rappaport, M. S.; Cuño, C. B. and George, J. Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models. Journal of Neuroinflammation, 18:19, 2021.
Gowran, A.; Noonan, J. and Campbell, V. A. The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. CNS Neurosci. Ther. 17, 6, 637–644, 2011.
Heemels, M. T. Neurodegenerative diseases. Nature 539, 179, 2016.
Karelina, T.; Lerner, S.; Stepanov, A.; Meerson, M. and Demin, O. Monoclonal antibody therapy efficacy can be boosted by combinations with other treatments: Predictions using an integrated Alzheimer’s Disease Platform. CPT: Pharmacometrics & Systems Pharmacology, 10, 8, 2021.
Nishibori, M.; Mori, S. and Takahashi, H. K. Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases. Journal of Pharmacological Sciences, 140, 1, 94-101, 2019.
Sauer, A. The Effects of Medical Marijuana on Alzheimer’s Treatment. Published 2016. Disponível na Internet: http://www.alzheimers.net/6-15-15-effects-of-medical-marijuana-on-alzheimers/. Xing, H., Y.; Li, B.; Peng, D.; Wang, C. Y.; Wang, G. Y.; Li, P. et al. A novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer’s disease. PLoS ONE 12(6), 2017.
Watt, G.: Karl, T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front. Pharmacol. 8 (FEB):1–7, 2017.
The Use of Monoclonal Antibodies in Treatment of Alzheimer Disease Hemen Moradi-Sardareh1, Maryam Moradi2, Elham Bordbar3, Mohammadreza Malekpour4, Sara Bagheri5, Nasrin Nakhodazadeh6, Shahin Rahbar7, Javad Farhadian Asgarabadi8, Meysam Ebrahimi Far9
Budd, H. S.; O'Gorman, J.; Chiao, P. et al. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. The Journal of Prevention of Alzheimer's Disease, 4(4):255-263, 2017.
Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells – Salk Institute for Biological Studies. Published 2016.
Currais, A.; Quehenberger, O.; Armando, A. M.; Daugherty, D.; Maher, P. and Schubert, D. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. npj Aging and Mechanisms of Disease (2016).
Fassler, M.; Rappaport, M. S.; Cuño, C. B. and George, J. Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models. Journal of Neuroinflammation, 18:19, 2021.
Gowran, A.; Noonan, J. and Campbell, V. A. The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. CNS Neurosci. Ther. 17, 6, 637–644, 2011.
Heemels, M. T. Neurodegenerative diseases. Nature 539, 179, 2016.
Karelina, T.; Lerner, S.; Stepanov, A.; Meerson, M. and Demin, O. Monoclonal antibody therapy efficacy can be boosted by combinations with other treatments: Predictions using an integrated Alzheimer’s Disease Platform. CPT: Pharmacometrics & Systems Pharmacology, 10, 8, 2021.
Nishibori, M.; Mori, S. and Takahashi, H. K. Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases. Journal of Pharmacological Sciences, 140, 1, 94-101, 2019.
Sauer, A. The Effects of Medical Marijuana on Alzheimer’s Treatment. Published 2016. Disponível na Internet: http://www.alzheimers.net/6-15-15-effects-of-medical-marijuana-on-alzheimers/. Xing, H., Y.; Li, B.; Peng, D.; Wang, C. Y.; Wang, G. Y.; Li, P. et al. A novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer’s disease. PLoS ONE 12(6), 2017.
Watt, G.: Karl, T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front. Pharmacol. 8 (FEB):1–7, 2017.
The Use of Monoclonal Antibodies in Treatment of Alzheimer Disease Hemen Moradi-Sardareh1, Maryam Moradi2, Elham Bordbar3, Mohammadreza Malekpour4, Sara Bagheri5, Nasrin Nakhodazadeh6, Shahin Rahbar7, Javad Farhadian Asgarabadi8, Meysam Ebrahimi Far9
Neurodegenerative diseases pose a major threat to human health. These age-dependent disorders are becoming increasingly prevalent, in part because the elderly population has increased in recent years
