Trial Shows Canakinumab Prevents Cancer and Heart Attacks by Reducing Chronic Inflammation

Summary: Physicians implicate chronic inflammation as a cause of cancer and heart disease. In a recent trial, patients given the inflammation-lowering drug Canakinumab enjoyed a nearly a 25% decrease in heart attacks and almost a 50% decrease in cancer. [This article first appeared on LongevityFacts under the title ‘ Can We Prevent Cancer and Heart Attacks by Reducing Chronic Inflammation?’ and was updated on Dec. 17, 2017. Author: Brady Hartman]

Doctors implicate chronic inflammation as a cause of heart disease and cancer with some claiming that reducing persistent, low-grade inflammation will reduce these diseases. In fact, a recent clinical trial discovered that the inflammation-lowering drug Canakinumab reduced heart attack and strokes by nearly a fourth and cancer by about half.

More than ever, physicians believe that reducing chronic inflammation will also reduce heart attacks and strokes. Robert A. Harrington, M.D., a Cardiologist with the Department of Medicine at Stanford University, leans toward the inflammatory hypothesis of heart disease, a belief that chronic inflammation is a significant cause of heart disease. According to Dr. Harrington

“Inflammatory cells and signals drive the healing response to vascular injury, allowing the initiation and growth of atherosclerotic plaque.”

In turn, the cardiologist feels, the plaque build-up and inflammatory processes significantly increase the likelihood of heart attack.

It’s important to know what chronic inflammation is, what causes it, and how it can harm your heart, and how you can stop it.

Chronic Inflammation

We typically think of inflammation occurring after an injury or an infection, which is accompanied by a red or swollen joint. Inflammation is a process in which the body releases infection-fighting chemicals and white blood cells to aid in the body’s healing process. Think about a splinter in your finger. Our bodies launch an attack with white blood cells and chemicals that result in redness and swelling to kill the intruder.

However, inflammation can also be a long-term problem in which the body releases low levels of these same chemicals and white cells. Doctor’s suspect that this low-grade chronic inflammation is caused by being overweight, having overly high levels of blood sugar and not being physically active. Although it is not proven yet that inflammation directly causes cardiovascular disease, chronic inflammation is common among heart disease and stroke patients and is closely linked to atherosclerosis, a condition that underlies stroke, heart attack, and peripheral artery disease.

Scientists are still researching the role that inflammation plays in heart attack and stroke, suspecting it is the inciting event in many heart attacks. Like the splinter example earlier, chronic inflammation can damage your heart. Cigarette smoking elevated blood pressure, and high cholesterol can injure the heart. In turn, atherosclerosis can develop, a condition in which fatty deposits called plaque build-up in the inner walls of arteries. This narrows the arteries and increases the risk they’ll become blocked. The American Heart Association (AHA) states that, among the many risk factors,

“High blood pressure is a major risk factor for heart disease and stroke. When your blood pressure stays within healthy ranges, you reduce the strain on your heart, arteries, and kidneys which keeps you healthier longer. High cholesterol contributes to plaque, which can clog arteries and lead to heart disease and stroke.”

The body perceives plaque as a foreign invader. In response, the immune system tries to wall off the plaque from the flowing blood. Occasionally, that plaque may rupture, and its walled-off contents enter the blood and trigger a blood clot. This combination of plaque and blood clots causes the majority of heart attacks and some types of stroke if the blood clot happens to block blood flow to the heart or brain. When an artery feeding the heart becomes blocked, it causes a heart attack. If an artery feeding the brain becomes blocked, it causes a stroke. 

The Inflammatory Hypothesis

Research published just last month adds weight to the inflammatory hypothesis, adding weight to the theory that chronic inflammation is a major contributor to heart attacks and strokes.

In late August, researchers reported the results of the four-year CANTOS Trial, testing an anti-inflammatory drug called Canakinumab. The CANTOS researchers found the drug reduced heart attack risk by one-fourth, while at the same time cutting the risk of cancer in half, and also protecting against inflammation-linked diseases such as arthritis and gout. Canakinumab works by decreasing chronic inflammation. The CANTOS study has added a substantial amount of evidence to support the inflammatory hypothesis, as Dr. Harrington pointed out

“CANTOS has helped move the inflammatory hypothesis of coronary artery disease forward scientifically.

Marvel Molecule Also Stops Inflammation

Canakinumab is not the only way to reduce inflammation. Scientists have developed a compound called MCC950 that turns off chronic low-grade inflammation, also called chronic inflammation, without interfering with the body’s natural defenses against infection.

Called a “marvel molecule” by some, researchers found that the molecule reduces heart attack damage in pigs and multiple sclerosis and inflammation in mice. The researchers from the University Medical Center Utrecht, in the Netherlands, reported their results in the European Heart Journal in March of this year.

Since their discovery, competing groups of scientists are racing to develop the compound for use in humans, to fight against inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, atherosclerosis, Parkinson’s disease and Alzheimer’s disease.

The Dutch researchers reported that the marvel molecule works by blocking inflammasomes, a complex of molecules that trigger inflammation when exposed to stress or infection. MCC950 works by blocking the NLRP3-inflammasome, a critical pathway in nearly all inflammation processes.

Related article: Researchers discover an ‘off-switch’ to body’s inflammation machinery.

Reduces Heart Damage, Even If You Eat Like A Pig

The Dutch researchers treated thirty pigs with the experimental drug for a week, and then artificially induced heart attacks in the pigs. When they examined the pigs, the researchers found that the MCC950-treated pigs had significantly reduced damage. The molecule acted to block the inflammation that accompanies a heart attack, and thus blocks some of the damage. Heart attacks, known as myocardial infarctions (MI), are one of the leading causes of death in mankind.

Pigs are considered to be one of the best models to test heart disease treatments. Regarding anatomy, size, pigs are similar to humans. A matured hog heart, for example, is about the size of an adult human heart. Pigs are a favorite of heart researchers because according to a widely quoted study, they “exhibit coronary artery anatomy and gross anatomic structure very similar to that of humans.”

Results Are Promising

The Dutch authors reported that the results of the compound are promising.

“NLRP3-inflammasome inhibition reduces infarct size and preserves cardiac function,”

The authors showed the compound has potential to reduce the damage caused by heart attacks (MI), adding

“Hence, NLRP3-inflammasome inhibition may have therapeutic potential in acute MI patients.”

What Are Inflammasomes?

In 2015, a group of researchers from Shangai discovered that all inflammatory diseases share a common process called an inflammasome – tiny complex molecules involved in multiple conditions that involve inflammation. The important implication of this discovery is that inflammasomes are a convenient centralized target to attack chronic inflammation, and the diseases it accompanies at its roots.

The research team from Shanghai concluded that the inflammasome is involved in all inflammatory diseases, including multiple sclerosis, type 2 diabetes, Alzheimer’s disease, and atherosclerosis.

Publishing their findings in the journal Frontiers in Pharmacology, the authors confirmed that when the body is under attack by stress or pathogens, it forms inflammasomes, and these inflammasomes start the inflammatory process throughout the body, putting the body into full-blown fever and inflammation in order to annihilate the pathogen. The international team said that the inflammasomes were the key role player in all inflammation, regardless of the body part.

Once created, inflammasomes are like grenades, ready to explode whenever the immune system needs to escalate the fight against infecting and raise the level of inflammation. The only thing that keeps the inflammasome from exploding is a tiny protein, which acts as a pin in a grenade. Removing the pin activates the inflammasome, producing inflammation.

Irish Eyes Are Smiling

Over two decades ago, the drug giant Pfizer, developed MCC950 as a potential treatment for arthritis but discontinued its efforts to bring the drug to market, it for business reasons.

The excitement began again in early 2015 when an Irish research team discovered that the compound MCC950 blocks inflammation.

The Irish team tested the marvel molecule on blood samples from U.S. patients and found that the compound blocked a critical step in the process of inflammation. They published their findings in the journal Nature.

Shown in the picture above, lead scientists behind the discovery, Professor Luke O’Neill said,

“Drugs like aspirin or steroids can work in several diseases, but can have side effects or be ineffective.” adding: “What we have found is a potentially transformative medicine [MCC950], which targets what appears to be the common disease-causing process in a myriad of inflammatory diseases.”

Study co-author Dr. Rebecca Coll added,

“MCC950 is blocking what was suspected to be a key process in inflammation.”

Prof. Matt Cooper, excited about the prospects for the compound in the treatment of disease, pointed out that,

“MCC950 is able to be given orally and will be cheaper to produce than current protein-based treatments, which are given daily, weekly, or monthly by injection.”

Prof. Cooper added,

“Importantly, it will also have a shorter duration in the body, allowing clinicians to stop the anti-inflammatory action of the drug if the patient ever needed to switch their immune response back to 100% in order to clear an infection.”

MCC950 holds promise the treatment of inflammatory diseases such as heart disease, rheumatoid arthritis, atherosclerosis, gout, multiple sclerosis, Parkinson’s disease and Alzheimer’s disease.

What Can You Do About Chronic Inflammation?

Cholesterol-lowering medications called statins appear to reduce arterial inflammation, but doctors don’t whether it’s from cholesterol reduction or something else.

The American Heart Association (AHA) says to reduce chronic inflammation it’s critical to control the risk factors, such as cigarette smoking, high blood pressure and high LDL cholesterol that can lead to inflammation. The AHA recommends seven ways people can live a healthier lifestyle. The AHA encourages people to keep the following three risk factors under control: blood pressure, cholesterol, and blood sugar.

Most of us know that high cholesterol is not good for us. What few people don’t realize is that one in three adults have high cholesterol and half of them don’t get treatment, according to the latest research.

Click here to learn more about high cholesterol

Some people aren’t aware that high blood sugar is a third risk factor for heart disease. Most of the food we eat is turned into blood sugar that our bodies use for energy. The AHA states that over time, “high levels of blood sugar can damage your heart, kidneys, eyes, and nerves.”

Learn how to reduce blood sugar.

To lower the risk factors and reduce chronic inflammation, the AHA also recommends getting active, eating better, losing weight and stopping smoking.

The AHA dietary guidelines recommend a diet rich in whole grains, fruits, and vegetables as well as low in added sugar, salt, and saturated fats. The aim is to reduce the high levels of type 2 diabetes, obesity, high blood pressure and heart disease –  all of which increase chronic inflammation in the body.

Additionally, studies show that a diet low in saturated fats reduces inflammation levels by up to 10 percent. When statin therapy is added to the mix, that figure drops to 33 percent.  High-fiber, low-carbohydrate diets, such as a diet rich in fruits and vegetables, also reduce chronic inflammation. Essentially, by exercising more, losing weight, and improving cholesterol and blood pressure levels, we can significantly lower our risk of heart disease.

Bottom Line

The findings of the Dutch and Irish research teams, as well as the results of the CANTOS Study, lend weight to the inflammatory hypothesis of heart disease, which states that low-grade, chronic inflammation is a significant cause of heart attack and stroke.

Drugs that reduce chronic inflammation are currently in the pipeline. Until then, the best way to reduce persistent, low-grade inflammation is to adopt a healthy lifestyle, such as the AHA’s seven recommendations.

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References

Van Hout GP, Bosch L, Ellenbroek GH, de Haan JJ, van Solinge WW, Cooper MA, Arslan F, de Jager SC, Robertson AA, Pasterkamp G, Hoefer IE. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. European Heart Journal 2017 Mar 14;38(11):828-836. doi: 10.1093/eurheartj/ehw247. Link.

Jennifer A. Dixon, MD and Francis G. Spinale, MD, Ph.D. LARGE ANIMAL MODELS OF HEART FAILURE: A CRITICAL LINK IN THE TRANSLATION OF BASIC SCIENCE TO CLINICAL PRACTICE.  Circ Heart Fail. 2009 May; 2(3): 262–271. doi:  10.1161/CIRCHEARTFAILURE.108.814459. Link.

Bo-Zong Shao, Zhe-Qi Xu, Bin-Ze Han, Ding-Feng Su, and Chong Liu. NLRP3 inflammasome and its inhibitors: a review. Frontiers in Pharmacology. 2015; 6: 262.  Published online 2015 Nov 5. doi:  10.3389/fphar.2015.00262 PMCID: PMC4633676.

Coll, R.C., Robertson, A.A.B., Chae, J.J., et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine 21(3), 248-255 (2015).

Disclaimer

Diagnosis, Advice, and Treatment:  This article is intended for informational and educational purposes only and is not a substitute for professional medical advice. The information provided in this report should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Experimental drugs such as canakinumab and MCC950 that treat chronic inflammation are not FDA approved and present additional risks when compared to approved drugs. Consult a licensed physician for the diagnosis and treatment of any and all medical conditions. Call 911, or an equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed physician before changing your diet, supplement or exercise programs.  Photos, External Links & Endorsements: This article is not intended to endorse companies, organizations or products. Links to external websites, depiction/mention of company names or brands, are intended only for illustration and do not constitute endorsements.

Tags: Cancer, Futurism, Heart disease, Inflammation