The Diabetes Epidemic

Diabetes is one of the largest health problems in the world. In its 2016 Global Report on Diabetes, the World Health Organization (WHO) estimated that 422 million people worldwide have the disease – 314 million more than in 1980. Approximately 8.5% of adults worldwide have diabetes. Approximately $920 billion is spent annually in the treatment of diabetes and related healthcare. Over 20% of healthcare dollars in the U.S. are estimated to be spent on care for people with diagnosed diabetes. Up to 29.1 million people in the U.S. have diabetes. Approximately $615 million was spent annually in treatment of diabetes alone. The worldwide market for diabetes treatment has been projected to reach $650 billion by 2020.

Diabetes

Diabetes is caused by insufficient availability of, or resistance to, insulin. Insulin is produced by the islet cells of the pancreas. Its function is to assist in the transport of sugar in the blood to the inside of most types of cells in the body where it is used as a source of energy for those cells. In Type 1 diabetes the islet cells of the pancreas have been destroyed – usually by an autoimmune reaction. Type 1 diabetics require daily insulin administration through injection or through the use of an insulin pump. In Type 2 diabetes the body does not use insulin properly. This means the body has become resistant to insulin. Type 2 diabetes can generally be controlled by diet and exercise in its early stages. As time goes by, it may be necessary to use antidiabetic drugs to control the disease. However, over time these too may lose their effectiveness. Thus, even Type 2 diabetics may become insulin-dependent.

Efforts to Cure Diabetes

In an effort to “cure” Type 1 diabetes, replacement of damaged pancreatic islet cells has been attempted. This involves transplantation of the entire pancreas or of its beta islet insulin-producing cells. In 2000, islet cells from human cadavers were transplanted into 7 insulin-dependent diabetics in a clinical trial carried out in Edmonton, Canada. The procedure was known as the “Edmonton Protocol.” Each patient enrolled remained insulin-independent for one year. But because of the high doses of immune-suppressive drugs that must accompany such transplantations, patients were placed at high risk of infection and even cancer. These drugs have serious side effects and have required patients to cease treatment with them. Worldwide, less than 1,000 people with Type 1 diabetes are known to have been transplanted with pancreatic islets from another human.

Attempts to avoid the use of islet cells from human donors, have led to islet cells from pigs being used. This type of interspecies transplantation is known as xenotransplantation. Drug regulatory authorities have shown resistance in approving the use of such interspecies transplantations. In addition, there are problems besides regulatory approval, the foremost of which is an attack by the body’s immune system on the transplanted cells. To protect the non-human cells from attack by the immune system of the human being, they have been encapsulated using other forms of encapsulation technology than we use. In those studies, the transplanted islet cells from pigs were surrounded by a s capsule typically made of alginate (a derivative of seaweed).

However, to translate this concept into a viable treatment for Type 1 diabetes, researcher’s efforts have been plagued by poor survival of the transplanted islet cells. In addition, the integrity of capsules composed of alginate has been shown to degrade over time. This then allows for immune system attack on the transplanted pig islets and necessitates additional transplantations. Also, as the alginate “capsules” degrade, they can elicit an immune response.

Different tubular and planar “chamber-type” immune-protective devices that contain islet cells are under development by other companies. These devices are placed in the body where they can be retrieved and replaced when necessary. Tubular chambers have shown good biocompatibility, but they are subject to rupture, exposing the islets to immune system attack. They also require large numbers of islet cells. Planar chambers are more stable, but they can cause extensive foreign body reactions in the host resulting in fibrotic overgrowth and thus transplant failure.

The most extensively researched immune-protective strategy is that which employs microcapsules. They are relatively simple to manufacture, can be implanted into the body without major surgery and, depending on the nature of the encapsulation material, micro-encapsulated cells can be cryopreserved. Micro-encapsulated islet cells first made their appearance in 1994 when a diabetic patient, already receiving immunosuppressive drugs, was transplanted with these cells encapsulated in alginate and remained insulin-independent for 9 months. However, 22 years and numerous clinical trials later, there are still no reports of long-term insulin-independence in non-immune-suppressed diabetic patients receiving encapsulated pancreatic islet transplants.

PharmaCyte’s Bio-Artificial Pancreas for Diabetes

We plan to develop a therapy for Type 1 diabetes and insulin-dependent Type 2 diabetes that is unique among available therapies for this disease. We are developing a therapy that involves encapsulation of a human liver cell that has been genetically engineered to produce, store insulin and release insulin on demand at levels in proportion to the levels of blood sugar in the human body. The encapsulation will be done using the Cell-in-a-Box® technology.

In a “proof-of-principle” study of the effectiveness of the Cell-in-a-Box® encapsulation technology in developing a treatment for diabetes, Cell-in-a-Box® capsules containing pig pancreatic insulin-producing islet cells were transplanted into diabetic rats. Soon after the capsules were implanted into the rats, their blood glucose levels normalized and remained normal throughout the study period of six months. No immune system suppressing drugs were needed. Thus, the preclinical proof of principle for a bio-artificial pancreas has already been established using the Cell-in-a-Box® capsules containing pig pancreatic insulin-producing cells in a rat model of Type 1 diabetes.

In an effort to avoid the use of non-human islet cells in its diabetes treatment, PharmaCyte has obtained from the University of Technology Sydney (UTS) in Australia an exclusive, worldwide license to use insulin-producing genetically engineered human liver cells developed by UTS to treat Type 1 diabetes and insulin-dependent Type 2 diabetes. These cells, named “Melligen,” have already been tested in mice and shown to produce insulin in direct proportion to the amount of glucose in their surroundings. In fact, when Melligen cells were transplanted into immosuppressed diabetic mice, their blood glucose levels became normal. The Melligen cells reversed the diabetic condition.

Melligen cells can be readily grown in culture and are available in unlimited supply. Compared to native pancreatic beta islet cells, Melligen cells are much more resistant to the pro-inflammatory cytokines that have been shown to be involved in beta islet cell death. We believe that this property makes them an ideal candidate cell line for beta islet cell replacement therapy with the prospect to achieve long-term transplant graft function.

PharmaCyte has acquired from Austrianova an exclusive, worldwide license to use the Cell-in-a-Box® technology for the development of a treatment for diabetes. We believe that encapsulating the Melligen cells using Cell-in-a-Box® live cell encapsulation technology has numerous advantages over encapsulation of cells with other materials, such as alginate. Since our capsules are composed largely of cellulose (a bio-inert material in the human body), the Cell-in-a-Box® capsules are durable, resilient and long-lasting when compared to the competition. They remain intact for long periods of time in the body, all the while protecting the cells inside them from immune system attack. Also, in prior studies these capsules and the cells inside them have not caused any immune or inflammatory responses like those seen with alginate-encapsulated cells. Studies have shown that the Cell-in-a-Box encapsulation process does not reduce the capability of the Melligen cells to produce insulin.

We believe that the combination of the Melligen cells and the Cell-in-a-Box® encapsulation technology could lead to a breakthrough therapy for Type 1 diabetes and insulin-dependent Type 2 diabetes. Encapsulating the Melligen cells could enable us to overcome all of the past problems in developing a true bio-artificial pancreas. Members of our International Diabetes Consortium (see under “Company” tab), are working in concert to develop our therapy for insulin-dependent diabetes.