Brian Balin Philadelphia College of Osteopathic Medicine
Posted:
This article by Wozniak et al. addresses a very important question of pathogen involvement in AD, as well as a rationale for clinical trials testing antiviral therapy. This work demonstrates the association of virus and the accumulation of Aβ amyloid and p-tau and the relationship to viral replication. In addition, a number of antiviral drugs were shown to clear the virus and reduce the presence of the pathological entities, thereby suggesting that treating for the virus would be helpful in treating AD. Ruth Itzhaki and her group have been the leaders of these investigations for 20 years, and have provided significant information to establish a relationship between HSV1 infection and AD. These data warrant clinical trial approaches based on pathogen involvement in this disease. The benefit-to-risk ratio is quite high, given the specificity of the antivirals. The key questions are when to administer the drugs, what should be the duration of administration, and what outcome to measure. If we accept that amnestic MCI is a precursor to frank AD, the suggestion would be to treat at least at this stage. In addition, recognizing that the population is vulnerable to AD, even preclinically, individuals known to be infected with HSV1 at different ages could be enrolled in trials and followed prospectively. Given failure after failure of trials based on outcomes of pathology (i.e., amyloid and tau accumulation), antiviral trials would effect upstream events that could prevent downstream damage.
Interestingly, this approach brings into focus a key process in the pathological scheme, that being the generation of inflammation and subsequent damage. HSV1, and possibly other infectants, stimulate inflammatory processes in both the intracellular and extracellular environments that are key to damage in the nervous system. The generation of pro-inflammatory cytokines such as IL-1β and others would precede other pathologies observed in AD. This is contrary to the belief that amyloid is the key stimulus to inflammation (only downstream would this be the case). Inflammation from infection could lead to subtle changes to nerve cell functioning prior to irreversible damage, even to mild cognitive change. In effect, at this stage, if the stimulus (pathogen) was blocked (antiviral/antibiotic) and non-steroidal anti-inflammatories were on board (trials demonstrating usefulness prior to disease), blocking progression to defined disease could be achieved. Why shouldn’t we try?
I am a caretaker for my husband and have a medical background, having been the administrative assistant of the medical director of Sterling Drugs, Inc., and a hospital specialist for Pennwalt Prescription Products. I therefore am qualified and capable of reading medical papers with a certain degree of comprehension.
There is general acknowledgement that treatment for Alzheimer's/dementia is palliative rather than providing any true benefit. Furthermore, although there is acknowledgement that amyloid plaque and tangles are involved, when these are addressed directly, there is still no cognitive improvement. Recently, I have read numerous studies regarding the possibility that the plaque and tangles are protective mechanisms for the brain as an immune response. Now we find that the herpes virus may, in fact, be involved.
Given the urgency of doing something to stop this devastating disease in its tracks, and perhaps even the hope of reversing it, I see no reason why prophylactic antiviral therapy should not be administered before there is general consensus within the medical community. Brian Balin is right. Those who have loved ones who are afflicted by this horrific disease cannot afford to wait.
Comments
Philadelphia College of Osteopathic Medicine
This article by Wozniak et al. addresses a very important question of pathogen involvement in AD, as well as a rationale for clinical trials testing antiviral therapy. This work demonstrates the association of virus and the accumulation of Aβ amyloid and p-tau and the relationship to viral replication. In addition, a number of antiviral drugs were shown to clear the virus and reduce the presence of the pathological entities, thereby suggesting that treating for the virus would be helpful in treating AD. Ruth Itzhaki and her group have been the leaders of these investigations for 20 years, and have provided significant information to establish a relationship between HSV1 infection and AD. These data warrant clinical trial approaches based on pathogen involvement in this disease. The benefit-to-risk ratio is quite high, given the specificity of the antivirals. The key questions are when to administer the drugs, what should be the duration of administration, and what outcome to measure. If we accept that amnestic MCI is a precursor to frank AD, the suggestion would be to treat at least at this stage. In addition, recognizing that the population is vulnerable to AD, even preclinically, individuals known to be infected with HSV1 at different ages could be enrolled in trials and followed prospectively. Given failure after failure of trials based on outcomes of pathology (i.e., amyloid and tau accumulation), antiviral trials would effect upstream events that could prevent downstream damage.
Interestingly, this approach brings into focus a key process in the pathological scheme, that being the generation of inflammation and subsequent damage. HSV1, and possibly other infectants, stimulate inflammatory processes in both the intracellular and extracellular environments that are key to damage in the nervous system. The generation of pro-inflammatory cytokines such as IL-1β and others would precede other pathologies observed in AD. This is contrary to the belief that amyloid is the key stimulus to inflammation (only downstream would this be the case). Inflammation from infection could lead to subtle changes to nerve cell functioning prior to irreversible damage, even to mild cognitive change. In effect, at this stage, if the stimulus (pathogen) was blocked (antiviral/antibiotic) and non-steroidal anti-inflammatories were on board (trials demonstrating usefulness prior to disease), blocking progression to defined disease could be achieved. Why shouldn’t we try?
I am a caretaker for my husband and have a medical background, having been the administrative assistant of the medical director of Sterling Drugs, Inc., and a hospital specialist for Pennwalt Prescription Products. I therefore am qualified and capable of reading medical papers with a certain degree of comprehension.
There is general acknowledgement that treatment for Alzheimer's/dementia is palliative rather than providing any true benefit. Furthermore, although there is acknowledgement that amyloid plaque and tangles are involved, when these are addressed directly, there is still no cognitive improvement. Recently, I have read numerous studies regarding the possibility that the plaque and tangles are protective mechanisms for the brain as an immune response. Now we find that the herpes virus may, in fact, be involved.
Given the urgency of doing something to stop this devastating disease in its tracks, and perhaps even the hope of reversing it, I see no reason why prophylactic antiviral therapy should not be administered before there is general consensus within the medical community. Brian Balin is right. Those who have loved ones who are afflicted by this horrific disease cannot afford to wait.
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