Cholesterol-Lowering Vaccine May Immunise People Against Heart Disease
What is the main cause for human
suffering and deaths worldwide? Until recently, it used to be infectious
diseases. But in the last 15 years or so, heart disease has taken the
helm, becoming responsible for a quarter of deaths each year,
There are many approaches to prevent diseases. Among them, the use of effective vaccines is popular, effective and desirable. Vaccination is the administration of antigenic material to induce an individual’s immune system to develop antibodies to a pathogen. It is a time-tested technique a and long-lasting method to prevent infectious diseases. A vaccine against cardiovascular disease has not been not available until now – although that may soon change.
A study published recnetly has become the first of its kind to show that it is possible to immunise genetically modified mice with a molecule that causes the body to produce antibodies against PCSK9 (proprotein covertase subtilisin/kexin type 9), an enzyme that plays a pivotal role in preventing the clearance of low density lipoprotein (“bad”) cholesterol from the blood.
This enzyme binds to the low-density lipoprotein receptor and enhances its degradation. This leads to the reduced clearance of low-density lipoprotein (LDL) and a higher risk of atherosclerosis, a disease in which plaque builds up inside the arteries.
In the present study, researchers evaluated a vaccine, dubbed AT04A anti-PCSK9, for its therapeutic potential to ameliorate or even prevent coronary heart disease in the APOE*3Leiden.CETP mouse model. These are genetically modified mice for human-like lipid metabolism. Their response to lipid-lowering and high-density lipoprotein increasing interventions is similar to that of humans.
Impressive results in mice
According to a press release , “At present, drugs such as statins can be used to lower LDL cholesterol, but they have to be taken on a daily basis and although they are generally well-tolerated they can cause adverse side effects in some people. The most recently approved cholesterol-lowering compounds are monoclonal antibodies targeting PCSK9, which are highly effective, but their effect is short-lived, resulting in frequent reapplication and high costs.”
Researchers fed the vaccine-treated mice with a fatty Western diet for 18 weeks. They then monitored the antibody titres, plasma lipids and inflammatory markers by advanced, analytical procedures. They found that AT04A vaccine induces an effective immune response against PCSK9 in APOE*3Leiden.CETP mice, leading to a significant reduction of plasma lipids, systemic and vascular inflammation and atherosclerotic lesions in the aorta, the main artery.
They concluded that the vaccine might represent an effective approach for the treatment and even prevention of cardiovascular disease. But will it also be economic, as they claim? There is little doubt that the cost of the vaccine is bound to be prohibitive to the many who will need it. For example, a treatment regimen involving either alirocumab and evolocumab, both inhibitors of the PCSK9 enzyme, has been estimated to cost very high, which most patients won't be able to afford.
Nonetheless, the results of using the vaccine were very impressive. Also according to the release, “The AT04A vaccine, when injected under the skin in mice … reduced the total amount of cholesterol by 53%, shrank atherosclerotic damage to blood vessels by 64% and reduced biological markers of blood vessel inflammation by 21-28%, compared to unvaccinated mice.” It added that the antibodies introduced by the vaccine had “remained functional over the whole study period” and that “concentrations were still high at the end of the study.”
“If these findings translate successfully into humans, this could mean that, as the induced antibodies persist for months after a vaccination, we could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster,” the release quotes one of the study’s authors as saying. “This would result in an effective and more convenient treatment for patients, as well as higher patient compliance.”
He also told this correspondent that that they were currently performing a phase-one clinical trial to immunise people, and that the final results will become available in early 2018.
Potential side effects
He explained, “The way that AT04A is administered is comparable to a vaccine. However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body – pathogens – whereas AT04A induces antibodies against a target protein that is produced by the body: endogenous proteins. Thus it is really an immunotherapeutic approach rather than a vaccine approach.”
He clarified that they hope to sell their drug commercially by 2023-2025 depending on the market and the geography.
Will potential side effects of the vaccine, such as type 2 diabetes, have to be considered before submitting the vaccine for approval? “Although it has been published that LDL lowering by either statins or PCSK9 blockers might be associated with a small increased risk in new-onset of diabetes, the impact of these drugs on glycemic control parameters in patients with diabetes mellitus still remains unclear,” he answered. “However, upcoming clinical studies using AT04 have to prove safety of this immunotherapeutic drug also in terms of new-onset of diabetes.”
The phase one trial underway with humans – which he mentioned earlier – commenced in 2015. In the trial, AT04A and another molecule, AT06A, were given to 72 healthy people to assess their safety and activity.
A professor of clinical and experimental medicine and an associate professor of medicine wrote in an editorial accompanying the mice study that the results appeared “promising”. However, they cautioned, “Safety, the response in humans and the very important but unknown long-term immune effects need to be very carefully addressed during the course of clinical development.”
They also noted that reductions in total cholesterol via statins and other drugs have been associated with an increase in new onset diabetes. “Therefore, potential safety concern for long-term lowering of LDL cholesterol with a vaccine directed against PCSK9 is the potential for an increased risk of new onset diabetes. In the short term, the LDL cholesterol lowering effect of statins and PCS9 inhibitors appears to far outweigh the risks of new onset diabetes,” they concluded.
this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on. https://gscrochetdesigns.blogspot.com. one can see my crochet creations https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes https://kneereplacement-stickclub.blogspot.com. for info on knee replacement
There are many approaches to prevent diseases. Among them, the use of effective vaccines is popular, effective and desirable. Vaccination is the administration of antigenic material to induce an individual’s immune system to develop antibodies to a pathogen. It is a time-tested technique a and long-lasting method to prevent infectious diseases. A vaccine against cardiovascular disease has not been not available until now – although that may soon change.
A study published recnetly has become the first of its kind to show that it is possible to immunise genetically modified mice with a molecule that causes the body to produce antibodies against PCSK9 (proprotein covertase subtilisin/kexin type 9), an enzyme that plays a pivotal role in preventing the clearance of low density lipoprotein (“bad”) cholesterol from the blood.
This enzyme binds to the low-density lipoprotein receptor and enhances its degradation. This leads to the reduced clearance of low-density lipoprotein (LDL) and a higher risk of atherosclerosis, a disease in which plaque builds up inside the arteries.
In the present study, researchers evaluated a vaccine, dubbed AT04A anti-PCSK9, for its therapeutic potential to ameliorate or even prevent coronary heart disease in the APOE*3Leiden.CETP mouse model. These are genetically modified mice for human-like lipid metabolism. Their response to lipid-lowering and high-density lipoprotein increasing interventions is similar to that of humans.
Impressive results in mice
According to a press release , “At present, drugs such as statins can be used to lower LDL cholesterol, but they have to be taken on a daily basis and although they are generally well-tolerated they can cause adverse side effects in some people. The most recently approved cholesterol-lowering compounds are monoclonal antibodies targeting PCSK9, which are highly effective, but their effect is short-lived, resulting in frequent reapplication and high costs.”
Researchers fed the vaccine-treated mice with a fatty Western diet for 18 weeks. They then monitored the antibody titres, plasma lipids and inflammatory markers by advanced, analytical procedures. They found that AT04A vaccine induces an effective immune response against PCSK9 in APOE*3Leiden.CETP mice, leading to a significant reduction of plasma lipids, systemic and vascular inflammation and atherosclerotic lesions in the aorta, the main artery.
They concluded that the vaccine might represent an effective approach for the treatment and even prevention of cardiovascular disease. But will it also be economic, as they claim? There is little doubt that the cost of the vaccine is bound to be prohibitive to the many who will need it. For example, a treatment regimen involving either alirocumab and evolocumab, both inhibitors of the PCSK9 enzyme, has been estimated to cost very high, which most patients won't be able to afford.
Nonetheless, the results of using the vaccine were very impressive. Also according to the release, “The AT04A vaccine, when injected under the skin in mice … reduced the total amount of cholesterol by 53%, shrank atherosclerotic damage to blood vessels by 64% and reduced biological markers of blood vessel inflammation by 21-28%, compared to unvaccinated mice.” It added that the antibodies introduced by the vaccine had “remained functional over the whole study period” and that “concentrations were still high at the end of the study.”
“If these findings translate successfully into humans, this could mean that, as the induced antibodies persist for months after a vaccination, we could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster,” the release quotes one of the study’s authors as saying. “This would result in an effective and more convenient treatment for patients, as well as higher patient compliance.”
He also told this correspondent that that they were currently performing a phase-one clinical trial to immunise people, and that the final results will become available in early 2018.
Potential side effects
He explained, “The way that AT04A is administered is comparable to a vaccine. However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body – pathogens – whereas AT04A induces antibodies against a target protein that is produced by the body: endogenous proteins. Thus it is really an immunotherapeutic approach rather than a vaccine approach.”
He clarified that they hope to sell their drug commercially by 2023-2025 depending on the market and the geography.
Will potential side effects of the vaccine, such as type 2 diabetes, have to be considered before submitting the vaccine for approval? “Although it has been published that LDL lowering by either statins or PCSK9 blockers might be associated with a small increased risk in new-onset of diabetes, the impact of these drugs on glycemic control parameters in patients with diabetes mellitus still remains unclear,” he answered. “However, upcoming clinical studies using AT04 have to prove safety of this immunotherapeutic drug also in terms of new-onset of diabetes.”
The phase one trial underway with humans – which he mentioned earlier – commenced in 2015. In the trial, AT04A and another molecule, AT06A, were given to 72 healthy people to assess their safety and activity.
A professor of clinical and experimental medicine and an associate professor of medicine wrote in an editorial accompanying the mice study that the results appeared “promising”. However, they cautioned, “Safety, the response in humans and the very important but unknown long-term immune effects need to be very carefully addressed during the course of clinical development.”
They also noted that reductions in total cholesterol via statins and other drugs have been associated with an increase in new onset diabetes. “Therefore, potential safety concern for long-term lowering of LDL cholesterol with a vaccine directed against PCSK9 is the potential for an increased risk of new onset diabetes. In the short term, the LDL cholesterol lowering effect of statins and PCS9 inhibitors appears to far outweigh the risks of new onset diabetes,” they concluded.
this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on. https://gscrochetdesigns.blogspot.com. one can see my crochet creations https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes https://kneereplacement-stickclub.blogspot.com. for info on knee replacement
Labels: Cholesterol, heart diseases, lowering, Protect, statins, type 2 diabetes, vaccines
posted by G S Iyer at 10:21 AM
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