Technology Summary

About Us:

Arterez (pronounced arter-eaze) is a Michigan-based, bio-pharmaceutical company focused on the research, development and commercialization of a first-in-class platform of diagnostic bio-markers (panels) and a triple compound oral therapy targeting cardiovascular disease (CVD/CHD).

CVD diagnostics and drugs currently available broadly target symptoms of cardiovascular disease, rather than the multi-factorial root causes.  Technologies and innovations have advanced rapidly, including new diagnostics and therapeutic paradigms that render, in some cases, the current standard of care, obsolete.. We believe Arterez' platform technologies will play a significant role in the 'rapid evolution' toward predictive, preventive and curative solutions for CHD/CVD, vastly improving and extending life for millions worldwide.

The Problem:


Problem #1: Cardiovascular disease (CVD), particularly coronary heart disease (CHD) remains the No. 1 disease killer and keeps rising in the US and the world. By 2030, 23.6 million people are predicted to die from CVD (World Heart Federation report). In the U.S., 42% of all deaths annually are a direct result of CVD; one person dies every 33 seconds from heart disease. and it is the leading cause of death for all Americans, age 35 and older. (CDC, NCHS. Underlying Cause of Death 1999-2013 -Vital Statistics Cooperative Program).  


Problem #2: Current drugs target symptoms. For example, the symptom of hypertension is treated with diuretics, ACE inhibitors, ARBs, Ca antagonists, β-blockers; lipidemia, treated with statins, bile-sequestrants, fibrates, niacin; and, blood pooling, treated with anti-platelets, anti-coagulants, fibrinolytics. These symptom-targeted drugs are at best palliative.


Problem #3: The “war on cholesterol” to treat CVD has permeated the core of everyday life including policy makers, insurers, health care providers, clinicians, diagnostics, Wall Street, etc. Moreover, AHA/NIH research funding focuses on cholesterol may discourage alternative drug targets (2018. Gen Eng Biotech News: 38:8)


Problem # 4: Lack of alternative drugs perpetuates the lore of ‘cholesterol drug’ including new PCSK9 inhibitors.


We believe and can demonstrate the following:


  • cholesterol is not the cause of atherosclerosis in humans and is instead due to dysfunctional blood flow, disruption of the vessel’s protective coat (glycocalyx), inflammation and oxidation leading to atheroma (plaque). 

  • targeting cholesterol (boost ‘good cholesterol’, lower ‘bad cholesterol’) we believe is a misguided hypothesis for CVD treatment, while again Cardiologists and Physicians are not responsible, and merely working with the tools amd guidelines available to them.

  • humans do not become hypercholesterolemic by eating cholesterol – this only occurs in familial hypercholesterolemia (FH) patients with a defective gene that prevents cholesterol absorption (akin to increased LDL cholesterol in the bloodstream of cholesterol-fed rabbits due to  lack of cholesterol 7a) - hydroxylase that converts cholesterol to bile.

  • Chronic inflammation creates ‘tiny gaps’ in the membrane, subsequently leading to electrolyte leakage and osmotic imbalance and a family of CVD (e.g., hypertension, CHD, heart failure, etc.)  Moreover, osmotic imbalance results in blood debris infiltration and plaques. (Plaque definition: accumulation of inflammatory macrophage within the arterial walls).


We have developed and patented synthetic compounds that target the multifactorial root cause of CVD formulated as a triple combo and found to be both preventive and curative of plaque in preclinical Animal testing.


Arterez initial product innovations:


  • Embotricin™ (triple drug combo: repairs glycocalyx, anti-oxidant, anti-inflammatory)

             » prevents and reverse/shrinks plaque

  • GlycoCardia™ (4-7 blood biomarker panel)

             » measures glycocalyx disruption/integrity, plaque & clotting

























Nature of cardiovascular disease:


Cardiovascular disease consists of a family of diseases affecting both arteries and veins: diseases in the arteries include coronary heart disease (CHD), myocardial infarction (MI), stroke, hypertension, atrial fibrillation, congestive heart failure (CHF), congenital heart condition, and peripheral arterial disease (PAD); and in the veins are deep venous thrombosis (DVT) and pulmonary embolism (PE). Microorganisms are the first life forms on Earth, but it was only in the 1930s that they were discovered as root cause of infectious disease, which led to the development of the antibiotics. Before antibiotics, the available drugs against infectious disease were an array of symptom-targeted drugs including wine, soybean, myrrh, opium, iodide, mercury, arsenic, sulfa (2006. Infectious disease epidemiology: theory and practice. Publisher: Jones & Bartlett).


Much like microorganisms, the existence of glycocalyx was discovered more than 50 years ago (1966. Fed Proc 25:1773–1783), but the significance of this structure was not recognized, partly because it is destroyed upon conventional tissue fixation and not seen in most light microscopic examinations. Glycocalyx is a protective lining at the surface of the endothelium found in every healthy blood vessel, which is made of proteoglycan (a complex network of protein (glycoprotein) and disaccharide sugar (glycosaminoglycan). This complex network forms a dynamic layer between the flowing blood and the endothelium, continuously changing in thickness depending on shear or blood flow pressure. Thus, the shear generated by blood flow regulates the balance between biosynthesis and shedding of the various glycocalyx components. The core protein groups of this layer are syndecans and glypicans promiscuously bound with different glycosaminoglycan including heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan or hyaluronic acid (2007.Pflugers Arch; 454: 345–359).


Today, the glycocalyx is recognized as a key structure for maintaining vascular wall integrity. Any disruption or decrease in thickness results in chronic vascular disease (2010. Cardiovascular Research. 87: 300 – 310); for example chronic stagnant blood flow, common in bifurcated section of the arteries, triggers glycocalyx shedding and plaque formation. In the heart, disrupted glycocalyx in the coronaries result in poor blood flow (coronary perfusion); at the arteriolar level, a damaged glycocalyx slows down blood flow and decrease nitric oxide (NO) production creating constrictive vessel; and, at the capillary level, disrupted glycocalyx reduces blood flow to tissues or muscles. In addition, the glycocalyx harbors a wide array of enzymes that regulate proper blood flow including. superoxide dismutase (SOD), an enzyme which neutralizes reactive oxygen species; antithrombin (AT-III), a natural anticoagulant (blood thinner); and, lipoprotein lipase (LPL), an enzyme that releases triglycerides from chylomicrons and very low-density lipoproteins (VLDL) for energy. 


In stagnant blood, contaminants (bacterial infections, pollutants, etc) or debris congregate, which attract immune cells like monocytes and white blood cells (WBC). These immune cells release inflammatory cytokines and oxidative free radicals or reactive oxygen species (ROS). Over time, chronic inflammation and oxidative damage disrupt the protective glycocalyx lining of the blood vessel and create ‘tiny gaps’ on the endothelial wall. The “tiny gaps” in the arterial lining creates an osmotic imbalance, allowing infiltration of blood debris; accumulation of debris produce sticky or adhesive material (e-selectin) and along with macrophages (activated white blood cells) they form a “sticky foam cell” complex, which altogether attempt to plug a leaky wall. Such sticky cells recruit other blood debris (e.g., dead cells, calcium, fibers), which matures into plaque (atheroma). The processes leading to atheroma (atherosclerosis) generally begin in the early years of life, as young as 5 years old, but the symptoms generally do not become apparent until after the age of 40 years. Although members of the CVD family are totally different in clinical presentations, they are basically atherosclerosis-related and share a common feature, which is the plaque.


A natural sequence osmotic imbalance is edema (fluid buildup) and (concentration of solution). Thus, electrolytes that normally reside outside the cell (extracellular)  like sodium (Na), potassium (K), calcium (Ca), chloride (Cl), and bicarbonate (HCO3), leak through the ‘gap’ from the outside to inside of the cell, while electrolytes normally found inside the cell, such as potassium (K), magnesium (Mg), and phosphate (PO4) leak through outside towards the interstices. These electrolyte imbalance create various circulatory abnormalities most notably hypertension, heart failure, and venous blood clots.


The majority of plaques are stable and harmless; some ruptured plaques results in intra plaque hemorrhages (bleeding into the lipid core) but heals naturally (1994 BrMed Bull. 1994; 50:789-802). Plaque ruptures when the endothelial glycocalyx is denuded exposing the highly thrombogenic constituents (lipids, tissue factor, collagens) to the blood stream and activate the coagulation or thromboembolic cascade (1988. Br Heart J 60:459–465). Thromboembolism is a process leading to the formation of thrombus (blood clot), which dislodges from its origin to form an embolus that flows downstream in the blood vessel tree and clogs up blood flow. Thrombus is a solid mass consisting of platelets, fibrin and blood components; embolus is a piece of thrombus broken free and carried into the bloodstream, which is the fatal component in CVD: loose thrombus wedges on a rigid arterial vessel narrowed by hypertension, causing stroke (clogged artery to the brain), heart attack (clogged artery to the heart), or pulmonary embolism (PE) (clogged pulmonary artery).  


Plaque disruption has been studied most extensively (particularly in coronary arteries) to establish correlations between the morphology of the culprit plaques, degree of thrombus formation and types of ensuing ischemic coronary syndromes (1996. Circulation 94:2013–2020).  In coronary arteries of patients with severe pre-existing stenosis, occlusive embolus is fatal (1989. Br Heart J 50:127–134). The concept is that plaques with an unstable morphology are the main risk factor for coronary heart disease (CHD). On the other hand, most plaques that develop during a lifetime remain unnoticed and have no clinical implications at least on the short term. However, plaques may grow in the long term through the stimulant effect of blood components like thrombin and platelet-derived growth factor (PDGF). These large plaques may rupture but remain clinically silent (1989. Eur Heart J 10:203–208). Conversely, not all acute cardiovascular events are the result of plaque rupture (1996. Heart 76:112–117), but even smaller non-occluding thrombi may lead to clinical symptoms (1992. N Engl J Med;26:242–250). Because of its complexity and the clinical sequelae, atherosclerosis continues to be the main subject in pathology research.

Our patented and patent pending portfolio summary:


ComboRx™ (3-combo drugs)                                                          GlycoTRx™ (Diagnostic Panels)


Embotricin™: cardiovascular disease (CVD                                    GlycoCardia™

                            (FTX-214, -218, -219)

Metabotricin™: metabolic syndrome/diabetes                             GlycoDiabx™

                           (FTX-214, -216, -218)

Arthritricin™: arthritis                                                                           GlycoArthrx™

                           (FTX-214, -216, -224)


GlycoCardia™:   novel, diagnostic blood markers:


We evaluated a number of biomarkers including soluble fibrin (SF), thrombin-antithrombin complexes (TAT), and several others forcused on glycocalyx  remnants. We found 7-total markers resuting in a 4-5 marker panel or panels correlative to multiple atherosclerosis indications, particularly plaque formation.  All are patent pending.

GlycoCardia™ test kits can be fully tested and ready for market within 30-months of the start of test kit development.  Using standard ELISA laboratory equipment already available in most acute and clinical labs, adoption of the test will not be difficult and will be easily implemented. In 2014, there were 701,000,000 Lipid Panel tests run in the US alone. The lipid panel was designed to test a patient’s risk of CVD, focused on cholesterol and triglyceride, which are not predictive. Total cholesterol is an indication of the amount of lipoproteins in circulation and not a direct measurement of the family of cardiovascular diseases that may be present. Many recent studies have demonstrated that patients with both low and high total blood cholesterol readings have the same rate of death from CVD and related diseases.


The near-term application of the GlycoCardia™ diagnostic kit is CVD. However, as outlined in our development schedule, we will be creating algorithms enabling us to address other chronic diseases including diabetes, metabolic syndrome, arthritis, and neurodegenerative diseases.


Glycocardia™ highlights:

  • Provides specific information concerning the associated pathology and risk factors for the entire family of CVD and CHD Diseases.

  • Unique and proprietary blood test algorithm

  • Easily adoptable ELISA test structure; utilizes already existing equipment found in both acute and chronic care settings.

  • Proved to predict onset of clot and production of plaques in tested animals.

  • There is currently no diagnostic test available to medical practitioners providing patient specific information concerning the pathology or the absolute risk factors for the family of CV Diseases. 


Embotricin™ (pronounced embo-try-seen)


The current standard of care for CVD focuses around cholesterol-lowering statins as the drug of choice. Statins effectively lower cholesterol, but contrary to what has been claimed for decades, statins do not have a significant effect in primary or secondary prevention of CVD. Moreover, there are serious safety concerns tied to statins, prompting the FDA to issue new warnings (May, 2016) due to risks of memory loss, diabetes, cancer, and muscle pain. Cholesterol and triglyceride (TG) lowering treatments manage symptoms of CVD, at best, but do not effectively treat the disease as evidenced by the extraordinarily high death rate. Clearly, there is a need for a preventative and curative CVD drug.


Embotricin™ is a novel, first in class atherosclerosis therapy with unique mechanisms of action, which is both preventative and curative. Whereas an infectious disease is caused by a single agent and typically respond to a single drug (antibiotic); a chronic disease including CVD is multifactorial and therefore a correspondingly multi-component drug is needed for effective treatment. The etiology of CVD starts with disruption of the blood vessel lining, particularly the endothelial glycocalyx, followed by oxidative damage and a cascade of inflammation, creating osmotic imbalance resulting in plaques and atherosclerosis. Embotricin™ is a triple combo drug that addresses the multifactorial causes of CVD; it is the first ever anti-thromboembolic pill proven to be effective in preventing and eliminating plaque formation in our proprietary (mice) animal model of CVD.  Moreover, it is an oral, non-toxic drug with a safety index of 20X the effective dose.


The triple drug combo is a novel approach to drug development. We synthesized 8 novel drugs, which can be franchised in the development of curative drugs against other chronic diseases including diabetes, metabolic syndrome, arthritis, cancer, and neurodegenerative diseases.


    Therapeutic Highlights

  • Consists of three components, formulated as one pill and administered orally.

  • The effective human dose of each component (Based on animal trials) is 50 mg. and toxicological testing has shown that the maximum tolerated dose (MTD) is at least 750 mg/kg which is 15X greater than the effective dosage.

  • The first anti-thromboembolic drug to address the root cause of the family of CV Diseases and particularly Coronary Heart Disease, a breakthrough therapy with a medical impact equivalent to penicillin.

  • Repairs the endothelial glycocalyx, the newly recognized lining of the vascular endothelium, which when disrupted starts cardiovascular diseases (CVD), of which coronary heart disease (CHD) is the most common

  • First in class pill that targets thromboembolism (clotting or thrombosis), which is the ultimate cause of death in CHD and CVD

  • Both prophylactic and therapeutic activity

  • Pre-clinical animal testing demonstrated safety and efficacy

  • Direct replacement for and eliminates the need for statin therapies in ~90% of patient population

  • Embotricin™ is the first ever, non-toxic anti-thromboembolic pill proven to be effective in animal testing. Embotricin™ effectively and specifically protects, repairs and prevents damage to the arterial lining which is known to be the root cause of the family of cardiovascular diseases – the Endothelial Glycocalyx.  Embotricin™ prevents endothelial glycocalyx disruption as well as arterial oxidation and inflammation.     

Arterez Hypothesis


Our proposal involves the development of diagnostics and therapies against cardiovascular disease (CVD) focusing on the prevention of clot formation or thromboembolism. Technically, clot refers to either thrombus or embolus: thrombus in toto reduces flow of blood, while embolus is a broken thrombus that clogs up blood flow in downstream vessels and is the fatal component of CVD.




CVD is the major worldwide cause of mortality and a plethora of interventions have been tried with minimal reduction in risk (2017. J Royal Soc Med Cardiovasc Dis 6: 1–9). CVD is a family of blood vessel diseases involving the arterial and venous systems: the arterial system, which includes coronary heart disease (CHD), myocardial infarction (MI), stroke, hypertension, atrial fibrillation, congestive heart failure (CHF), peripheral arterial disease (PAD) and congenital heart condition (CHC); and, the venous system includes chronic venous insufficiency (CVI) and deep vein thrombosis (DVT). The common cause of death in these blood vessel diseases is clot formation or thromboembolism and clearly, cholesterol is not the cause of thromboembolism. The long-standing “cholesterol hypothesis”, which mandates maintaining a low blood cholesterol level has not delivered the promise of preventing CVD. Despite the widespread use of statins and cholesterol-lowering strategies, CVDs are the number 1 cause of death globally: more people die annually from CVDs than from any other cause. An estimated 17.9 million people died from CVDs in 2016, representing 31% of all global deaths; of these deaths, 85% are due to heart attack and stroke. CHD is the leading cause of death in the U.S. with an estimated 720,000 new attacks and 335,000 recurrent attacks annually. 


To appreciate the origin of diseases, we start by understanding our make-up (Fig. 1).

Figure 1. Our body is made of cells that regularly die and regenerate (except the neurons); cell regeneration, growth and repair, need energy.

Nourishing our body comes from the food that we eat; metabolism extracts electrons from stored C-H (e.g., carbohydrates, proteins, fats, alcohol) bonds (Fig 2).

Figure 2. Mitochondria is the power house of every cell that generates electrons to power the activities of

the cells


Oxygen that we breathe pulls food electrons in the mitochondria, via the electron transport system (ETS), creating electron flow (current or electricity); consequently generates energy in the form of adenosine triphosphate (ATP). However, ETS has a ‘glitch’ in that it leaks ~ 3% of food electrons. Leaked electrons over time interact with oxygen and generate more reactive oxygen species (ROS); such ROS steal electrons from molecules in our body (process called oxidation). These are intrinsically produced ROS and beneficial to a certain extent. However, exposure to stressful environmental factors contributes additional ROS, and these extraneous ROS would soon create an excessive level (Fig 3).

Fig. 3. The environment provides a varied source of chemicals that stress our cells, including infections ozones and chemicals packaged in particulate matters (PMs)

The intrinsically produced ROS are needed as signaling molecules for growth and repair and the right balance is kept in check by antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Peroxiredoxin (PRX) and glutathione reductase (GSR). However, excessive ROS level disrupts the ROS-antioxidant balance or homeostasis and results in the various diseases (Fig 4).

Figure 4. Excess reactive oxygen species (ROS) steal electrons, oxidize cellular molecules and trigger diseases and aging


The World Health Organization (WHO) was tasked to compile a listing of diseases called the International Classification of Diseases (ICD). In the 1994 ICD-9 there were 13,000 disease entries, which jumped to 68,000 in the updated ICD-10 in 2015. A jump in the disease entries is accounted for by the increasing exposure to environmental pollutants and chemicals that are artificial to our body (xenobiotics), creating diseases herein we call xenodiseases™. Basically, diseases could be grouped into three classifications (Fig. 5).

Figure 5. Diseases are basically grouped in 3 classifications


Indeed, a 25-year study has finally confirmed xenobiotics as the central cause of chronic diseases or Xenodiseases (Fig 6).

Figure 6. Chronic diseases (xenodiseases™) are now found to be triggered by environmental pollutants we have coined as Xenobiotics.


A review of the top diseases in a 16-year span (2000 – 2016) shows CVD as the top disease: chronic diseases kept rising, while infections were down. Notably, HIV and preterm birth infections disappeared from the chart. An infectious disease is invariably caused by a single microorganism and developing a drug (antibiotic or vaccine) against a single causative agent is straightforward and relatively easy. On the other hand, a chronic disease is multifactorial in nature with multiple symptoms and traditionally drugs are developed to target a symptom; symptom targeting drugs are not curative, palliative at best (Fig. 7).

Figure 7. Snap shot of the top 10 global diseases in a 16-year span, 2000-20016


Elevated blood cholesterol is singled out as the symptom associated with CVD and that lowering cholesterol became a consensus, albeit misguided, target for treating CVD. Currently, cholesterol-lowering drugs, particularly statins, are the number one prescription drugs and Lipitor the all-time revenue-generating pharmaceutical product (Fig 8)

Figure 8. Statins are the most prescribed and best-selling pharmaceuticals to treat CVD


Cholesterol is an integral part of our cells (Fig. 1); it is a key to life and a wrong drug target. For example, statins inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase responsible for cholesterol synthesis and corollary metabolic pathways needed for health (Fig. 9).

Figure 9. Statins disrupt cholesterol synthesis leading to a host of diseases, contributingto the growing problem of drug-related deaths.


Cholesterol supply disruption by statins or other factors has contributed to the growing list of xenodiseases™. Unbeknownst to most, drug-related complications, are now the leading cause of deaths in humans (Fig 10).

Figure 10. The number cause of deaths is drug-related, and growing


Actually, high cholesterol is needed in defense to stress:

  • cholesterol levels of  300-400 mg/dL range in response to stress (1999. J. Clin. Endocrinol Metab.  84, 2664–2672; 2002. J. Clin. Endocrinol. Metab.  87, 4872–4878)

  • under chronic stress, synthesis of LDL is increased to generate cortisol (2015. Afr  Health Sci.15: 131–136; 2009. J Ayub Med Coll Abbottabad.21:158-61) high cholesterol essential vs infection, respiratory diseases, depression, hemorrhagic stroke, etc. (1998. Epidemiol Infect 21:335–47)

  • cholesterol needed for cell growth and repair (2016 J: Biomed Spectroscopy Imaging, 5: S101-S117) statins do not have significant effect in primary and secondary prevention of CVD     (2015. Rev Clin Pharmacol 6: 1-11).

  • statins effectively lower cholesterol but not in treating atherosclerosis (2015. J Controversies Biomed Res 1:67-92)


Stress comes in many forms, including psychological, trauma, infections and xenobiotics. Our body combats stress by producing cholesterol, particularly cortisol (hydrocortisone) (Fig. 11).

Figure 11. High cholesterol is a symptom of stress, a natural defense to stress and infections


An elevated supply of cholesterol (LDL) is needed to combat stress level. However, chronic exposure to stress and failure to produce compensatory levels of LDL results in adrenal fatigue and the following diseases:

  • reduced insulin/glucose – diabetes (2013 Trends Pharmacol Sci 34 518–530)

  • reduced immunity – infection (2006. Int J Infect Dis 10:343-353)

  • reduced  calcium – osteoporosis (2010. Arch Biochem Biophys 503:137-45)

  • low water/salt retention – hypertension (2010. Arterios Thromb Vasc Biol 33 e39–e46)

  • low progesterone – PMS, uterine fibroids, breast cancer   (2013. Ann Rev Physiol75:225-240)

  • dysfunctional lipid – CVD, obesity (2003. Microsc. ResTech.  60, 76–84).


Another source of adrenal fatigue is natural sequelae to aging. As we age the capacity of our sexual organs (ovaries, testes) to produce cholesterol hormones diminish e.g., for women, 4 types of estrogens (estradiol, estrone, estriol, estetrol) and, testosterone for men. After the age of 40, the adrenal glands assume the double duty of producing stress hormone (cortisol) and estrogens to meet the needs of our body; overworked adrenal glands leads to adrenal fatigue. Hormone replacement therapy (HRT) was designed to alleviate the overworked adrenal gland and to combat adrenal fatigue. However, each woman has varying levels of exposure to daily stress, infection, pollution and chemicals making it difficult to individually optimize HRT dosing, thereby the HRT-related diseases (Fig. 13).

Figure 13. Hormone replacement therapy (HRT) is a strategy to supplement estrogen,but individual experience to daily stressors complicate its effectiveness


In regards to cholesterol’s role in CVD, the association of elevated level of blood cholesterol and CVD was borne of an experiment by a Russian scientist (Ignatowski) who fed meat, eggs and milk to a rabbit and observed arterial lesions.  Rabbits, being herbivore, do not have the innate ability to metabolize meat products including fat and cholesterol, consequently they accumulate in the circulation and deposited as arterial lesions (Fig 14).

Figure 14. Feeding rabbit with meat allowed ‘packaged cholesterol and fat’ to pile up in blood artery forming ‘foam cells’ that matures into plaque


This serendipitous experiment was misconstrued to happen also in humans, which established the consensus that dietary cholesterol leads to the development of atherosclerosis (“Cholesterol hypothesis”) in both animals and humans. This is a flawed hypothesis because humans are naturally equipped with an enzyme, cholesterol hydroxylase (CYP7A1), that converts cholesterol to bile and prevent cholesterol accumulation (Fig 15).

Figure 15. In humans, cholesterol hydroxylase (CYP7A1) converts cholesterol to bile. Meanwhile, fat-packaging VLDL (very low density lipoprotein) increases blood viscosity and blood flow stagnation.


Regardless, the rabbit became a de facto model in the study of the pathogenesis and development of human atherosclerosis (Fig 16).

Figure 16. The rabbit as the central animal model in studying cholesterol biosynthesis.


Other animals were tried to model atherosclerosis but only rabbits easily produced high cholesterol level on cholesterol- and fat-rich diet. The rabbit was the standard animal model until the creation of a mouse with a genetically deleted apoE gene (ApoE−/− mouse), which produced high cholesterol on a high-fat diet (Fig 17).

Figure 17. Historical use of rabbit and ApoE−/− mouse as models of atherosclerosis.


Dietary fats and cholesterol do not dissolve in water, thus they are packaged in lipoproteins for delivery to the blood stream, e.g., chylomicron, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). The protein portion of the lipoprotein is responsible for binding to specific receptors in the cells for absorption and delivery (endocytosis) of the packaged fat or cholesterol to the cells. Once VLDL unloads its fat cargo, it becomes IDL; subsequently, IDL unloads its fat cargo to become LDL, and unloading of fat from LDL becomes HDL. (Note: cholesterol is always packaged in lipoproteins; there is no free-floating cholesterol in the blood stream or free-cholesterol sticking onto arterial wall, and no such thing as “good- or bad-cholesterol”). The protein responsible for binding these lipoproteins to unload their cargo was initially designated as the arginine-rich peptide, but later renamed apoE. In an ApoE−/− mouse, the apoE gene was deleted (apoE knockout or apolipoprotein E-deficient), which prevents absorption of VLDL, IDL, HDL (Fig 18).

Figure 18 . Make up of lipoproteins and their function in delivering fats and cholesterol


In an ApoE−/− mouse,  the absence of the apoE binding protein allows the lipoproteins to circulate in the blood stream and overtime “stick” on the arterial wall resulting in hypercholesterolemia. Currently, the ApoE−/− mouse is the model of choice in the study of human atherosclerosis (Fig 19).

Figure 19 . ApoE−/− mouse genetically engineered to produce high level of blood cholesterol,now the consensus model of atherosclerosis


In summary, dietary fats and cholesterol are packaged in lipoproteins to assimilate them into the blood stream. Rabbits, being herbivores, do not have adequate enzyme system (cholesterol hydroxylase) to dispose these lipoproteins, which eventually accumulate as arterial ‘lesions’. On the other hand, mice and humans have adequate cholesterol hydroxylase to convert lipoproteins to bile to alleviate ‘backlog’.  To create a mouse that becomes hypercholesterolemic on high-fat/high-cholesterol diet, the apoE gene was deleted (ApoE−/− mouse, apoE knock-out mouse). In both rabbit and ApoE−/− mouse, the lipoproteins are not absorbed and linger in the arterial circulation to eventually produce atherogenic lesions. 


We have chronicled and analyzed the evolution of Statin drugs, from inception to present day in great detail, and are happy to share those findings upon request.

Arterez Platform


Figure 20. Anatomy of the protective endothelial glycocalyx, 


The average human has 60 – 100,000 miles of blood vessels consisting of straight and bifurcated segments. The dynamics of blood flow through these vessels is unimpeded in the straight segments but slows down at bends or bifurcations forming a ‘whirlpool’ flow. Conditions that increase blood viscosity (blood thickening) further slows down blood flow to a point of stagnation.


Dietary fats and cholesterol do not dissolve in water, thus to be absorbed into the blood stream they are packaged in lipoproteins, which include chylomicrons, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). In humans dietary cholesterol is packaged in chylomicron, delivered to the liver, subsequently converted (via cholesterol 7 alpha-hydroxylase or CYP7A1) and disposed as bile. On the other hand, dietary fat is packaged in VLDL for delivery to the cells as source of energy; high fat diet means high level of VLDL, which contributes to blood viscosity. After VLDL unloads its fat content, it becomes LDL, and as LDL unloads its fat, it becomes HDL (Fig. 9).


Stagnant blood pockets in the arterial system traps blood ‘contaminants’ (bacterial infections, pollutants, etc), which attracts monocytes releasing inflammatory cytokines and ROS. Stagnant pockets are exacerbated by excess dietary fats packaged in VLDL, which increases blood viscosity. Over time, chronic inflammation disrupts the protective endothelial glycocalyx; exposes endothelium to injury, forming ‘tiny gaps’. Blood debris (dead cells, chemicals, electrolytes, calcium, etc.) infiltrate these ‘tiny gaps’; activated macrophage follow these debris to form sticky adhesive material (e-selectin) or ‘foam cell’ Actually, such sticky foam cell is a defense mechanism of the body to plug the ‘tiny gaps’ which would  mature into plaque (Fig 21).  

Figure 21. Stagnant pockets deposits biological and chemical debris, which starts the oxidative-inflammatory cascade and atherosclerosis


The processes leading to plaque build-up (atherosclerosis) generally begin in the early years of life, as young as 5 years old, but the symptoms generally do not become apparent until after the age of 40 years.  A natural sequence to the ‘tiny gaps’ is edema (fluid buildup) and osmotic imbalance (concentration of solution). Thus, electrolytes that normally reside outside the cell (extracellular)  like sodium (Na), potassium (K), calcium (Ca), chloride (Cl), and bicarbonate (HCO3), diffuse inside through the ‘gap’. On the other hand, electrolytes normally found inside the cell, such as potassium (K), magnesium (Mg), and phosphate (PO4) diffuse out. These electrolyte imbalance create various circulatory abnormalities most notably hypertension, heart failure, and venous blood clots (Fig. 22).

Figure 22. Tiny gaps create osmotic imbalance allowing diffusion of electrolytes and a family of cardiovascular diseases (CVD)


The straight arterial segment with unimpeded blood flow has high shear stress, which is important in maintaining a thick protective glycocalyx layer. In segments of bends or bifurcations, the glycocalyx lining is typically thinner and prone to injury. Such bends are found in various parts of the vasculature including the brain, heart and limbs.


The coronary arteries have the most bends and bifurcations, which is the reason they are prone to plaque formation. Of the coronary arteries, the left anterior descending (LAD) has at least 4 bends and as many plaques accounting for CHD as the most prominent (~50%) of CVD cases (Fig 23).

Figure 23. Family of CVD as manifested in different parts of the vascular system


Further inflammation predisposes the plaque to rupture and ruptured plaque triggers clot (embolus) formation causing stroke (clogged artery to the brain), heart attack (clogged artery to the heart), or PAD (clogged artery to the arms or legs) (Fig 24).

Figure 24. Formation of clot starts with a disrupted glycocalyx (primary clot) and progresses into a secondary clot (embolus), this is the fatal component of CVD


In summary, interruptions to arterial blood flow causes blood stagnation where ‘blood debris’ gravitates (e.g., dead cells, ‘microbial contaminants’, etc). These attract monocytes, which produce oxidative (ROS) and inflammatory (cytokines) factors; chronic inflammation leads to destruction of the protective glycocalyx lining. Destruction of the glycoclyx exposes the endothelium to injury creating ‘tiny gaps’ in the endothelial wall, subsequently blood debris and macrophage infiltration to form plaques. Certain plaques become unstable by further inflammation and rupture; rupturing of plaque simulates an injury, which activates platelets that trigger thromboembolism causing heart attack or stroke.



Embotricin Targets 





CVD is a multifactorial disease involving: blood flow disruption, oxidation, inflammation and thromboembolism. In this regard, we constructed a flow chart to identify every possible site in the vasculature as drug targets

(Fig. 25)


Figure 25. The thromboembolic cascade and identified ‘druggable’ targets


Based on the targets and experience in active drug ingredients, we rationally synthesized drugs incorporating ingredients naturally found in body including:

  • Melatonin - Antioxidant , directly detoxifies ROS/reactive nitrogen species (RNS) , increases the activity of antioxidative enzymes while suppressing pro-oxidant enzymes in mitochondria, stabilizes the mitochondrial inner membrane

  • Xylose - serves as a primer for the formation of heparin/heparin sulfate and chondroitin/dermatan sulfate chains, which is initiated by the attachment of α-D-N-acetylglucosamine (GlcNAc) or β-D-N-acetylgalactosamine (GalNAc), respectively. The glucosaminoglycan (heparin/heparan sulfate) and the galactosaminoglycan (chondroitin/dermatan sulfate) chains then assemble by the alternating addition of GlcUA and GlcNAc or GlcUA and GalNAc, respectively.

  • Lipoate – Inactivates the nuclear factor kapp B (NF-κB that plays a crucial role in immune response, inflammation, cell growth and survival, and development, acts as powerful antioxidants. (1) quenching of reactive oxygen species (ROS)(2) regenerates the antioxidant capacity of several important antioxidants, including vitamin C , Vitamin E, Coenzyme Q10,  (3) chelation of metal ions, and (4) reparation of oxidized proteins.

  • Choline – acts in the synthesis of membrane phospholipids, specifically phosphatidyl choline (PC), which is the predominant phospholipid (>50%) in mammalian membranes.  PC is important in maintaining cellular integrity, and signaling functions.

  • Cysteine - an important source of sulfur, which forms the very reactive sulfhydryl (SH or thiol) group. Cys is a unique amino acid in that the thiol group binds to nearby sulfhydryl often crucial for the stabilization of and function of protein and enzymes.


Using the above ingredients, we synthesized eight (8) proprietary lead drugs designed to restore a healthy glycocalyx layer and prevent thromboembolism; these include drugs with antioxidant, anti-inflammatory, antimicrobial, and anticoagulant properties (Fig 26)

Figure 26. Eight proprietary drugs with corresponding drug targets


To evaluate the drug leads, we developed a mouse model that mimics cardiovascular disease and the thromboembolic cascade:  the Tunac Arterial Plaque (TAP) mouse™ model, (2017. J Clin Exp Cardiolog Suppl 8:1).  This involves feeding mice with high fat diet and exposure to biological and chemical agent (PCB). Indeed, we created a mouse that produced well-formed plaques (Fig 27).

Figure 27. The Tunac arterial plaque (TAP) mouse™ model, first time plaques were formed in a natural mouse


Our proprietary approach was not to administer the FTX-drugs as monotherapies, but as combo drugs formulated as one pill. The traditional drug development paradigm is one drug-one disease. However, the complex nature of thromboembolism does not lend to a one-drug treatment. Thus, in an abbreviated factorial design, we rationally formulated drug combinations (3-drug combos) and tested them in our animal model (Fig 28)

Figure 28. An abbreviated factorial 3-drug combo design. Note, individual drugs showed activity but combo FTX-214, -218, and -219 (K) was curative and preventive of plaques


Combo K is hereafter designated Embotricin™ (Ebn). Ebn was both preventive and curative as evidenced by the prevention or restoration of glycocalyx components including hyaluronan (HAS-1), heparan SO4 (HS), and syndecan-1 (SDC-1) Fig. 29.

Figure 29. Embotricin™ prevented and restored shedding of glycosaminoglycans, This corroborates the clinical data


Also, Embotricin™ was both curative and preventive of clot formation as evidenced by the marker plasminogen activator inhibitor -1 (PAI-1), which corroborates clinical data (Fig. 30).

Figure 30. Embotricin™ was curative and preventive of clot (embolus) formation as evidence by the marker plasminogen activator inhibitor-1 (PAI-1), 


Based on these experimental observations, the proposed mode of action of Embotricin™ includes restoration of the glycocalyx (FTX-214), anti-oxidant (FTX-218), and antiinflammatory (FTX-219) activities (Fig 31).

Figure 31. Possible action sites of the 3 Embotricin™ components: FTX-214, -218, and -219


Preliminary toxicological evaluation of Embotricin™ showed it to be non-toxic.The effective dose of Embotricin™ is 50 + 50 + 50 per 70 kg (average human weight), and toxicological testing showed that the maximum tolerated dose (MTD) could be as high as 750 + 750 + 750 mg/kg, with a tolerable dose of up to 2,000 mg/kg, which indicate the combo to be nontoxic (Fig 32)..

Figure 32. A 28-day escalating dose toxicity profile of Embotricin™


Diagnostic Bio-Markers

No single biomarker is predictive of a multifactorial disease thus a need for a panel: Our 4-panel GlycoCardiaCVD measures the level of glycocalyx disruption per levels of shed components (e.g., hyaluronan, heparan, syndecan) plus early clot formation (plasminogen activator inhibitor). These markers were robustly validated in the TAP mouse™ model to correlate with plaque formation. Members of our 3-panel GlycoCardiaHF were well-documented in the clinic for heart failure, hypertension and plaque rupture. We have a number of blood samples from patients clinically identified at different stages of CVD and in the process of creating algorithm or fingerprints for both GlycoCardiaCVD and GlycoCardiaHF (Fig 33).


Figure 33. Clinical proof-of-principle on the use of Glycocardia™ as diagnostic and predictive markers for CVD


Diagnosis of chronic diseases in the form of fingerprint is a first-in-class approach to accurately account for their multifactorial nature. Thus, a diagnostic panel is a fail-safe approach for predictive diagnosis of the various families of CVD. Moreover, a panel has the precision to stage CVD severity and a key companion diagnostic tool during the course of therapy.


With increasing incidence of CVD, individual cardiac markers are being developed and in huge demand. Physicians use cardiac markers in two ways: (1) in acute care to diagnose a cardiac event in a hospital emergency room, and (2) risk assessment to evaluate heart attack or stroke after they have occurred; these markers include creatine kinase-MB (CK-MB,) troponin, and myoglobin, and newerones such as C-reactive protein (hsCRP), homocysteine, Fatty Acid Binding Protein (FABP), Glycogen Phosphorylase isoenzyme BB (GPBB), urinary albumin, S-100 protein, and hemoglobin A1c (hbA1c). On the other hand, the traditional markers for risk evaluation include the Lipid panel (cholesterol test) with the addition of myeloperoxidase (MPO), brain natriuretic peptide (BNP). Since CVD is multifactorial in nature, the definition of a cardiac marker expands to a panel of various biomarkers according to specific cardiac conditions (e.g., stroke, thrombosis, heart attack, hypertension, atrial fibrillation, etc.).


The components of our GlycoCardia CVD and GlycoCardia HF are currently used individually in the clinic as putative diagnostic tools for various chronic diseases including CVD (Fig 34).   

Figure 34. The GlycoCardia™ is a panel of biomarkers currently used individually in the clinic.


In summary, the individual components of our drug Embotricin™, showed putative activities corresponding to their target, e.g., prevent glycocalyx shedding (FTX-214), antioxidant (FTX-218), and antiinflammatory (FTX-219); but only in combo did they synergistically become curative and preventive of plaque in our TAP™ mouse model. Likewise, our 7 biomarkers have individually proven in the clinic as important biomarkers but only in combo or panel can an algorithm or fingerprint be built, which make the GlycoCardia™ a first-in-class predictive and diagnostic tool. For example our 7 biomarkers have been clinically validated.


Current disease biomarkers are being used to validate the presence of disease after preliminary exam by a physician (reactive). On the other hand, our GlycoCardia panels are designed to be both proactive and predictive diagnostics. For example a panel fingerprint of low levels of markers represents start of the disease and higher levels for advanced stage (Fig. 35).

Proprietary information,

patent filings in process

Figure 35. Prototype GlycoCardia™ fingerprint and application to the diagnosis and treatment program


Thus the development pathway of a GlycoCardia™ kit involves testing fingerprinting of clinical samples that have been identified and sorted by a physician. An algorithm or fingerprint is created per statistical analysis to identify or diagnose new cases and serve as a guide for treatment programs (Fig. 36).

Figure 36. Development pathway and the making of a GlycoCardia “fingerprint”


GlycoCardia™ can be used twofold: 1) as a companion diagnostic for Embotricin™, or 2) ‘stand-alone’ diagnostic to monitor or evaluate the traditional symptom-targeted therapies for their ability to restore glycocalyx, clotting potential, mitigate hypertension, heart failure, stroke and CHD. The latter presents an immediate market for GlycoCardia™.  (Fig 37).  

Figure 37. Schedule use of GlycoCardia™ to monitor Embotricin™ or traditional treatment


In regard to our drug Embotricin™, our development pathway involves proof-of-principle (POP) clinical trial in selected hospital with a time frame of completion within 4years. This requires an Internal Review Board (IRB) and the POP to include three clinical targets: coronary heart disease (CHD), hypertension, and heart failure (Figs. 38, 39, 40).

Figure 38. Inclusion and exclusion criteria for Internal review board (IRB) proof-of-principle clinical trial for coronary heart disease (CHD)

Figure 39. Inclusion and exclusion criteria for Internal review board (IRB) proof-of-principle clinical trial for hypertension

Figure 40. Inclusion and exclusion criteria for Internal Review Board (IRB) proof-of-principle (POP) clinical trial for heart failure


Indeed, restoration of glycocalyx has been validated in clinical trial as a compelling treatment for heart failure (Fig 41).

Figure 41. The anatomy of heart failure and the numerous symptom-targeted drugs,which are at best palliative treatments


Besides CVD, the disruption of the glycocalyx has been associated with other chronic diseases. Thus, a 3-drug combo predicated by Embotricin™ will serve as a platform to develop our other drug leads (Fig 42)

Figure 42. Diseases triggered by the disruption of the glycocalyx





A number of compounds have been implicated in the reversal of plaques by restoring the health of the glycocalyx. The integrity of the glycocalyx is maintained by a balanced synthesis and shedding of its component parts. While excess shedding is associated with cardiovascular risks, it is possible to reverse shedding as shown in the following examples:

  • hydrocortisone (2010. Shock 34: 133-9)

    • protective against ischaemic injury & inflammation;

    • blocks synthesis of chemokines and heparanase.

  • direct inhibition of glycocalyx degradation:

    • Etanercept: inhibits glycocalyx degradation (2009.Atherosclerosis 2002:296-303)

    • Doxycycline antibiotic inhibits glycocalyx shedding (2009. Microcirculation16:657-66).

  • antithrombin III (2007. Shock 28(2):141-7)

    • inhibits serine proteases (thrombin and elastase) & coagulation

    • induce prostacyclin & prevent vascular leakage

  • supply of “prefab” components:

    • hyaluronan & chondroitin sulphate combo regenerates glycocalyx, and syndecan-1 heals post infarction damage of myocardium. (2010. Curr. Opin .Investig. Drugs11:997-1006)

    • heparin as anti-inflammatory & anticoagulant. (2011.Am. J. Respir. Crit. Care Med.183: A4172)

  • Sulodexide, a 3 small molecules combo: 80% heparan sulfate and 20% dermatan sulfate (like mesoglycan, borderline nutraceutical/drug) is a potent anticoagulant widely accepted as long-term, endothelial-protecting drug in many countries, except US (2015. Drug Des Devel Ther. 9:6275–6283); and proposed to improve endothelial dysfunction through reduction of vascular endothelial growth factor (2014. Drug Des Devel Ther. 8:49–65).

  • Arterosil®, a glycocalyx nutraceutical extracted from green seaweed, claimed to regenerate the glycocalyx and possess anticoagulant and antithrombotic activity (2015.Mar. Drug 13:2967-3028.13).


Embotricin™ is the first drug that systematically addresses glycocalyx restoration or repair and the other predisposing risk factors of CVD including oxidation and inflammation. The robust preclinical data may well prove Embotricin™ to be the first curative drug against chronic diseases with the same impact as penicillin to infectious disease (Fig. 43)   

Figure 43. Historical accounts indicating Embotricin™ to be a breakthrough discovery for the cure of cardiovascular diseases


Diseases are triggered by our lifestyle and the environment we live in; genetics has very little to do with diseases and longevity (2010. Nature. 467: 963–966)

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