|Addressing Unmet Medical Needs by Harnessing Complex Carbohydrate Chemistry|
|By David Platt, Ph.D. - CEO of Boston Therapeutics, Inc|
An Expert Briefing by David Platt, Ph.D., CEO of Boston Therapeutics, Inc.
Complex carbohydrate chemistry and diabetes
Carbohydrates have been shown to play a fundamental role in normal cell functions as well as in major disease pathologies including cancer, cardiovascular disease and inflammatory diseases. As a class of molecules, carbohydrates have an enormous range of shape, orientation and composition. Due to this structural diversity, carbohydrate chemistry can be applied to develop a broad range of complex therapeutic molecules and drugs, including pure carbohydrates as well as protein-linked carbohydrates, or glycoproteins. However, as a consequence of their structural complexity, carbohydrates have not received as much scientific attention as nucleic acids and proteins. However, significant progress is being made in this area.
Consider diabetes mellitus, a condition shared by nearly 26 million Americans and growing, according to the U.S. Centers for Disease Control and Prevention. As uncontrolled diabetes can lead to micro- and macrovascular complications, tighter but safe glycemic control is imperative. Interestingly, even as high carbohydrate intake can lead to a rise in blood sugar (glucose) and increase one’s risk of diabetes, research suggests that complex carbohydrate chemistry is one key to reducing the uptake of sugar into the bloodstream.
PAZ320 aims to lower post-meal elevation of blood glucose
Manchester, NH-based Boston Therapeutics (OTCQB: BTHE) is developing a non-systemic, non-toxic chewable complex carbohydrate-based compound named PAZ320 for its ability to lower post-meal elevation of blood glucose, and thus as a treatment to delay or prevent the onset of Type 2 diabetes and related complications such as heart disease, stroke, kidney damage, retinopathy and diabetic foot. The compound is a complex polysaccharide to be taken before meals; it operates in the gastrointestinal tract to block the action of carbohydrate-hydrolyzing enzymes that break down carbs in foods during digestion, lowering the amount of available glucose absorbed via the intestine.
Researchers have written a paper, slated to be published in the peer-reviewed journal Endocrine Practice, reporting positive Phase II clinical trial results of PAZ320 in patients with Type 2 diabetes. The study evaluated the combination of PAZ320 and oral agents or insulin in 24 patients with Type 2 diabetes between the ages of 18 and 75 with a body mass index of 25-40 kg/m2 and with HbA1c of less than or equal to nine percent. HbA1c is a lab test that shows the average level of blood sugar (glucose) over the previous three months.
Forty-five percent of patients responded with a 40 percent reduction of post-meal glucose in the blood compared to baseline in a dose-dependent manner. Additionally, results showed the effect of PAZ320 does not correlate with duration of diabetes and works regardless of concurrent diabetes medications. There was no severe hypoglycemia and gastrointestinal side effects were mild. Satiety also was observed. There were no serious adverse events from the data analysis of the open-label dose escalation crossover trial on Type 2 diabetic patients.
IPOXYN™ is designed to prevent necrosis
A separate potential application of carbohydrate chemistry is as an injectable anti-necrosis drug, both for the prevention of necrosis and the treatment of ischemic conditions that may lead to necrosis. Boston Therapeutics is developing this application under the name IPOXYN™. The drug consists of a stabilized glycoprotein composition containing oxygen-rechargeable iron, targeting both human and animal tissues and organ systems deprived of oxygen and in need of metabolic support.
Necrosis is the outcome of severe and acute injury. It is involved in many pathological conditions such as heart attack, brain injuries and stroke, neurodegenerative diseases such as Alzheimer’s dementia, Lou Gehrig’s disease (ALS), septic shock, liver cirrhosis, chronic hepatitis, pancreatitis, diabetes, acute or critical limb ischemia, gangrene, chronic pressure ulcers and many others. Necrosis occurs following ischemia (a shortage of oxygen supply to the tissue due to restriction in blood supply). The only treatment available at present for necrosis is providing oxygen by a high pressure facility. Thus, there is a crucial need to develop drugs for prevention and treatment of this pathology.
For decades, oxygen carriers have been developed for perfusion and oxygenation of ischemic tissue; none have yet succeeded. These products were either blood-derived elements, synthetic perfluorocarbons or red blood cell modifiers. Several of the Hemoglobin-Based Oxygen Carriers (HBOC) contained nonfunctional methemoglobin impurities. These products failed to secure FDA approval based upon either poor outcomes in clinical trials or poorly formulated product.
The new approach to treatment of ischemic tissue and prevention of necrosis is fundamentally different; it is a New Chemical Entity (NCE), not a biologic blood substitute, with a modified Heme chemical structure. The new compound prevents methemoglobin formation associated with the adverse effects of vasoconstriction and myocardial infarction. Furthermore, because of its extremely small molecular size, roughly 1/5,000th the size of a red blood cell, it is able to perfuse constricted, ischemic capillaries that are inaccessible to red blood cells. This small molecular size has particular significance in treating vascular complications of diabetes since red blood cells may already be enlarged and lower limb vasculature may be compromised. One such complication is limb ischemia, a chronic condition of severe obstruction of the peripheral circulation that results in severe pain in the extremities; lower-limb ischemia is a life-threatening complication for patients with poorly controlled diabetes and affects 10 percent of the diabetic population. The new compound is a glycoprotein-derived substance that is sourced from a biological mixture which is prone to immunologic activity, and the agent is purified by a novel processing technology. In general, the human body conserves the protein and recaptures amino acid moiety. The compound is broken down and eventually is collected in the spleen or liver, or it is simply eliminated by reversible endocytic processes in the kidneys.
OXYFEX™ is being developed to serve the veterinary market
A veterinary facsimile of Ipoxyn™, OXYFEX™, is also under development by Boston Therapeutics, reflecting an unmet need for blood replacement and oxygen delivery to damaged or ischemic tissue due to trauma, surgery, anemia and other disease conditions. This can work as an oxygen delivery mechanism for animals suffering ischemia or traumatic and surgical blood loss events.
In summary, complex carbohydrate chemistry, as it is being harnessed by Boston Therapeutics, is a key tool for addressing unmet medical needs in a variety of areas. Its continued development might offer new treatments and hope for millions of patients worldwide.
David Platt, Ph.D. is CEO of Boston Therapeutics, Inc., a pharmaceutical company focused on the development, manufacturing and commercialization of novel, carbohydrate-based compounds to address unmet medical needs in the areas of diabetes and inflammatory diseases. He can be reached at [email protected]