If I had a nickel for every headline like this that ultimately failed, like the technology, to actually achieve the promise, I would be on a tropical beach sipping pina coladas:
“Glucose monitoring for diabetes made easy with a blood-less method” (link)
Technologies in development for less-invasive or non-invasive glucose monitoring are legion, and many are very promising, but you can’t fill out a deposit slip with these promises. Frequently, such alternatives are based on the premise of quantifying blood glucose by sensitively detecting glucose in other fluids (interstitial fluid, tears, saliva, urine, etc.) that do not require the use of lancets to draw blood. However, despite their sensitivity and other sophistication in detecting minute quantities of glucose, their “arm’s length” to actual blood glucose compounds the challenge by requiring that the test reproducibly correlate the sample values with actual, current blood glucose levels.
The challenge stands unanswered, while the burgeoning population of endlessly finger-pricked diabetics remains painfully unsatisfied.
As a practical reality, continuous blood glucose monitors like those from Dexcom and Medtronic offer far more to the diabetic population, not only by avoiding finger pricks but also by revealing the patterns in blood glucose levels over time as a result of activity, carbohydrate intake, insulin bolus, insulin basal rate, stress and countless other patient-specific determinants.
The market for tissue engineering and cell therapy products is set to grow to nearly $32 billion by 2018. This figure includes bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration, products that often represent a combination of biotechnology, medical device and pharmaceutical technologies. The largest segment in the overall market for regenerative medicine technologies and products comprises orthopedic applications. Other key sectors are cardiac and vascular disease, neurological diseases, diabetes, inflammatory diseases and dental decay and injury.
An overview (map) of the spectrum of clinical applications in tissue engineering and cell therapy is shown below:
Cell therapy is defined as a process whereby new cells are introduced into tissue as a method of treating disease; the process may or may not include gene therapy. Forms of cell therapy can include: transplantation of autologous (from the patient) or allogeneic (from a donor) stem cells , transplantation of mature, functional cells, application of modified human cells used to produce a needed substance, xenotransplantation of non-human cells used to produce a needed substance, and transplantation of transdifferentiated cells derived from the patient’s differentiated cells.
Once considered a segment of biomaterial technologies, tissue engineering has evolved into its own category and now comprises a combination of cells, engineering and suitable biochemical and physiochemical factors to improve or replace biological functions. These include ways to repair or replace human tissue with applications in nearly every medical specialty. Regenerative medicine is often synonymous with tissue engineering but usually focuses on the use of stem cells.
Tissue engineering and cell therapy may be considered comprised of bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration. These often comprise a combination of biotechnology, medical device and pharmaceutical technologies.
Researchers have been examining tissue engineering and cell therapy for roughly 30 years. While some products in some specialties (such as wound care) have reached market, many others are still in research and development stages. In recent years, large pharmaceutical and medical device companies have provided funding for smaller biotech companies in the hopes that some of these products and therapies will achieve a highly profitable, commercial status. In addition, some companies have been acquired by larger medical device and pharmaceutical companies looking to bring these technologies under their corporate umbrellas. Many of the remaining smaller companies received millions of privately funded dollars per year in research and development. In many cases it takes at least ten years to bring a product to the point where human clinical trials may be conducted. Because of the large amounts of capital to achieve this, several companies have presented promising technologies only to close their doors and/or sell the technology to a larger company due to lack of funds.
The goal of stem cell research is to develop therapies to treat human disease through methods other than medication. Key aspects of this research are to examine basic mechanisms of the cell cycle (including the expression of genes during the formation of embryos) as well as specialization and differentiation into human tissue, how and when the differentiation takes place and how differentiated cells may be coaxed to differentiate into a specific type of cell. In the differentiation process, stem cells are signaled to become a specific, specialized type of cell when internal signals controlled by a cell’s genes are interspersed across long strands of DNA and carry coded instructions for all the structures and functions of a cell. In addition, cell differentiation may be caused externally by use of chemicals secreted by other cells, physical contact with neighboring cells and certain molecules in the microenvironment.
The end goal of stem cell research is to develop therapies that will allow the repair or reversal of diseases that previously were largely untreatable or incurable.. These therapies include treatment of neurological conditions such as Alzheimer’s and Parkinson’s, repair or replacement of damaged organs such as the heart or liver, the growth of implants from autologous cells, and even regeneration of lost digits or limbs.
In a developing human embryo, a specific layer of cells normally become precursor cells to cells found only in the central nervous system or the digestive system or the skin, depending on the cell layer and the elements of the embryo that direct cell differentiation. Once differentiated, many of these cells can only become one kind of cell. However, researchers have discovered that adult body cells exist that are either stem cells or can be coaxed to become stem cells that have the ability to become virtually any type of human cell, thus paving the way to engineer adult stem cell that can bring about repair or regeneration of tissues or the reversal of previously incurable diseases.
Another unique characteristic of stem cells is that they are capable of self-division and self-renewal over long periods of time. Unlike muscle, blood or nerve cells, stem cells can proliferate many times. When exposed to ideal conditions in the laboratory, a relatively small sample of stem cells can eventually yield millions of cells.
There are five primary types of stem cells: totipotent early embryonic cells (which can differentiate into any kind of human cell); pluripotent blastocyst embryonic stem cells, which are found in an embryo seven days after fertilization and can become almost any kind of cell in the body; fetal stem cells, which appear after the eighth week of development; multipotent umbilical cord stem cells, which can only differentiate into a limited number of cell types; and unspecialized adult stem cells, which exist in already developed tissue (commonly nerves, blood, skin, bone and muscle) of any person after birth.
Tissue engineering and cellular therapy products take years of research and many millions of dollars (averaging about $300 million, according to some reports) before they make it over the hurdles of clinical trials and into actual market launch. More than one small biotech company has burned through its money too quickly and been unable to attract enough investment to keep the doors open. The large pharmaceutical and medical device companies are watching development carefully, and have frequently made deals or entered into alliances with the biotechs, but they have learned to be cautious about footing the bill for development of a product that, in the end, may never sell.
For many of the products in development, product launch is likely to occur within five years. Exceptions include skin and certain bone and cartilage products, which are already on the market. Other products are likely to appear on the European market before launch in the United States, due to the presence of (so far) less stringent product review and approval laws in the European Union.
Even when the products are launched, take-up will be far from 100% of all patients with that particular condition. Initially, tissue engineering and cell therapy products will go to patients suffering from cancers and other life-threatening conditions, who, for example, are unable to wait any longer for a donor organ. Patients who seem to be near the end of their natural lives likely will not receive these treatments. Insurance coverage will certainly play a key role as well in the decision about who receives which treatments and when. But most importantly, physicians will be selecting who among their patients will be treated; the physicians learn about the treatments by using them, by observing the patient’s reactions, and by discussing their experiences with colleagues. In other words, the application of tissue engineering and cellular therapy will progress in a manner similar to the introduction of any new technology: through generally conservative usage by skilled, highly trained physicians dedicated to providing their patients with the best possible treatment without causing them additional harm.
Wound care product sales are growing at wildly variable rates around the world, with extremes spanning from the emergence of new technologies in rapidly growing economies to the technologies with low innovation in sluggish economies.
MedMarket Diligence’s global analysis of wound care products, technologies, companies and markets reveals the full spectrum of growth rates for well established to rapidly emerging products.
Below is illustrated the high growth country/product segments in wound management, reflecting the rapid adoption of new technologies such as growth factors and bioengineered skin, as well as older products such as alginates that are gaining sales in rapidly developing economies.
Source: MedMarket Diligence, LLC; Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”
At the other end of the extreme are those very well established products growing at less than anemic rates in countries where the economy is not as robust and/or where the growth has been superseded by sales of more novel products. Conventional dressings and bandages offer considerably less demand than do growth factors, bioengineered skin and skin substitutes and similar new products.
Of course, growth of sales in wound management products (and any product) is defined as the percentage change in sales volume over time. Smaller markets (typically soon after they have formed as a result of their initial commercialization) tend to grow on a percentage basis much faster. Indeed, a $1 dollar sale in year 1 followed by a $2 sale in year 2 represents a 100% growth rate, while a $1 increase in sales from year 1 to year 2 for a $100 million market represents virtually zero growth. Conversely, a 1% increase in a $1.75 billion market is a $17.5 million increase. This is indeed obvious, but must be kept in mind when considering the growth rates discussed above.
Recent research by scientists at Johns Hopkins University has found that patients with type I diabetes who use the advanced technologies of continuous blood glucose monitors and infusion pumps fare better then those patients who use finger stick blood glucose testing and insulin injection to, respectively, measure blood glucose levels and administer insulin.
In their study, Sherita Hill Golden, M.D., M.H.S., an associate professor in the division of endocrinology and metabolism at the Johns Hopkins, and her colleagues reviewed and re-analyzed data from 33 randomized controlled trials that compared the newer technologies to conventional methods of monitoring and controlling blood sugar levels. The new technologies they looked at were primarily real-time continuous glucose monitoring devices and insulin pumps.
The researchers found that children, teens and adults with type 1 diabetes who used continuous monitoring had lower blood glucose levels than those who used finger stick testing alone. They also spent less overall time with too much blood sugar (hyperglycemia). Both methods worked equally well to control hypoglycemia, the condition that results when blood sugar levels are too low.
While hypoglycemia was adequately managed by both conventional (finger stick and insulin injection) and advanced (insulin pumps and continuous blood glucose monitoring) methods, hyperglycemia was managed better with continuous blood glucose monitoring and insulin pump infusion. Since more frequent hyperglycemia correlates directly with higher HbA1C levels, overall type I diabetes management is therefore consider better with the more advanced technologies.
Diabetes management is moving toward the state when the combined use of continuous blood glucose monitors and infusion pumps — often described as the “artificial pancreas” — will be the norm for management of this disease, at least until the emergence of cost-effective and otherwise practical stem cell therapy or other pancreatic cell replacement, which may ultimately “cure” type I diabetes.
See the MedMarket Diligence report #D510, “Diabetes Management: Products, Technologies, Markets and Opportunities Worldwide 2009-2018” for a complete analysis of the worldwide market for diabetes diagnosis, management and treatment products.
The International Diabetes Federation released its latest findings on the global picture for diabetes, which is foreboding: 366 million diabetics worldwide (a 22% increase over 2009), an annual death count of 4.6 million, and a health care bill of 465 billion.
The diabetes market, which includes both pharmaceuticals and medical devices, is large, and is growing steadily for four main reasons. First, the prevalence of diabetes is increasing, particularly that of type 2 in developed countries and those with increasing prosperity. Type 1 diabetes is also increasing, though less dramatically. Second, type 2 diabetes is responsive to drug therapy, and there is a continuing search for newer, better pharmacological agents. Third, insulin, required for all cases of type 1 and some of type 2 diabetes, poses administration problems, offering opportunities for new delivery systems. Fourth, patients with diabetes must monitor their condition by frequently checking the level of glucose in their blood, and there are ongoing attempts to make this process easier and more user-friendly by developing more advanced (and expensive) devices.
A fifth driving factor in the diabetes marketplace is the search for a fundamentally better way to manage the disease. Some options are mainly surgicalâ€”transplants of pancreatic cells, for example. Another focus for research is to combine glucose monitoring with insulin administration in a self-controlled wearable device. And farther in the future are prospects for using stem cells to grow new beta cells, and for using genetic knockout techniques to block the metabolic processes that cause diabetes.
A Many-Sided Market
The diabetes market includes both pharmaceutical and medical device elements. The pharmaceutical aspect is again divided between insulin and oral antidiabetic drugs. The medical device aspect is made up of instruments for diagnosis and monitoring with their attendant consumables, and a range of devices for administering insulin. Some of these devices contain prepackaged insulin, so that they may be regarded as both medical devices and pharmaceuticals.
The global market for products in the management of diabetes is detailed in the MedMarket Diligence Report #D510, “Diabetes Management: Products, Technologies, Markets and Opportunities Worldwide 2009-2018.”
Research in the diabetes field has taken two main directions: improving current therapies, and exploring radical new approaches. Improvements in current therapy include making glucose monitoring and insulin delivery less invasive and more patient-friendly, and many significant advances have been made in this context in the past two decades. Among these have been the development of insulin pumps and of non- or minimally-invasive techniques for sampling blood. New, fast-acting forms of insulin have been introduced. There has been considerable research in non-injection dosage forms for insulin, and the first inhaled insulin product has recently been approved. This could herald a new era in insulin therapy.
Another ground-breaking development will be the successful development and regulatory approval of an “artificial pancreas.” This is the term used to describe a system in which continuous glucose monitoring is linked electronically to continuously variable insulin delivery, effectively making diabetes control automatic and freeing the patient to get on with his/her life. The technology behind an artificial pancreas is still being developed but it is at an advanced stage. While the major components — an insulin pump and a continuous glucose monitor — are already on the market, and as a combined system by one manufacturer (Medtronic), the FDA has not approved a unified system in which the system runs autonomously by glucose readings driving insulin infusion rates. The algorithms, software and other systems necessary are likely to gain approval in only 1-2 years.
More radical approaches to diabetes mellitus, also the subject of vigorous research, include ways of replacing the whole cumbersome business of glucose testing and insulin administration. Transplantation of healthy pancreatic islets into diabetic patients has been explored, but the problems of rejection are a significant hurdle. More promising is the modification of adult or embryonic stem cells so that they develop into pancreatic beta-cells capable of being implanted in the patient and serving as a replacement for the insulin-secreting cells that have been destroyed.
Further in the future are developments based on genetic manipulation. Several gene anomalies have been identified as related to the development of type 1 diabetes in particular, and these may present targets for intervention to prevent the disease from developing.
The global market for products in the management of diabetes (monitoring, anti-diabetic drugs and insulin) is a $5 billion market currently and is growing at over 9% annually, a rate that is unlikely to slow while rates of obesity prevalence keep climbing.
Please note that the original data on glucose monitoring referenced in the post below was compiled in mid-2010 — considerable change has taken place in the market since then.
One of the fundamental challenges in managing diabetes, especially insulin-dependent diabetes mellitus (or “juvenile onset” diabetes) is the lag between a sharp trend in blood glucose levels (up or down) and the diabetic’s awareness. The sooner a diabetic can become aware of becoming hypo- or hyperglycemic, the sooner he/she can act to preempt this adverse affects, some of which (especially for hypoglycemia) can be dangerous.
Couple this with another fundamental challenge in diabetes — the need for painful, frequent blood glucose testing involving finger pricks for blood sampling — and it becomes clear why continuous blood glucose monitoring (cBGM), especially non-invasive, holds potential. While the challenge of providing cBGM is currently more economic than technical, as a practical matter the solution has not yet emerged that is supported by industry.
Below (and in response to an inquiry from a Quora member) is a 2010 listing (perhaps in need of a recent update) of manufacturers developing continuous blood glucose monitors.
Developers of Continuous Blood Glucose Monitors
Advanced hypo- and hyperglycenia alarms. Has integrated FreeStyle meter for calibration