In a dramatic illustration of the potential for microbes to prevent disease, researchers have shown that mice exposed to common stomach bacteria are protected against the development of type 1 diabetes.
The findings support the “hygiene hypothesis” — the theory that a lack of exposure to parasites, bacteria and viruses in the developed world may lead to increased risk of diseases like allergies, asthma, and other disorders of the immune system.
The results also suggest that exposure to some forms of bacteria might actually help prevent onset of type 1 diabetes, which is an autoimmune disease. In Type I diabetes, the patient’s immune system launches an attack on cells in the pancreas that produce insulin.
With human trials proving promising, an Indian company is close to developing a shot-free insulin for diabetics.
For Abhinav Gupta, a 41-year-old middle-level executive at a private company in Delhi, each meal is an ordeal. Whether he is travelling or at home, everyday, before lunch and dinner, he has to inject a shot of insulin into a small fold of his skin on the abdomen in order to take care of the overload of glucose that reaches the bloodstream after every meal.
Gupta, like nearly 50 million Indians, suffers from type 2 diabetes, a lifestyle disease that is haunting both urban and rural India alike. In fact, his is an advanced case of diabetes and he suffers from an impaired pancreas, resulting in limited production of insulin, a hormone that helps stabilise the glucose level in the blood. As a result, he has to take insulin injections before every meal. Nearly 20 to 25 per cent of diabetics in India need insulin therapy, currently administered through either injections or an insulin pump that releases insulin regularly.
Those who suffer from Type 1 diabetes — or juvenile diabetes — too depend on periodic insulin infusion.
But for Gupta and millions of others who have to prick themselves for their daily dose of insulin, help may be soon on hand, with leading Indian biotech firm Biocon successfully completing phase-II trails of an insulin tablet. “We are pretty happy with the results and plan to begin phase-III clinical trials by early 2009,” says Harish Iyer, general manager for research and development at Biocon.
Biocon released the results of the trials at the recent European Association for the Study of Diabetes meeting in Rome. The primary target of the study was to establish the dosage of the drug, which the firm has codenamed IN-105. The study found that when 30 milligram of IN-105 was given to a diabetic patient, the blood glucose levels were nearly 50 milligram/decilitre lower than those who were given a placebo (a dummy pill without any active therapeutic ingredients).
“If everything goes well with the next round of clinical trials, we hope to introduce the oral insulin tablet sometime in 2010,” Iyer told KnowHow.
Biocon, which has been producing several medicines for diabetes, took up the project following its acquisition of the US firm Nobex Corporation, which made substantial progress in oral insulin in 2006.
Though attempted earlier, oral insulin delivery was found to be difficult because the hormone is easily digested by enzymes in the gut. As a result, very little insulin actually reaches the bloodstream.
If oral insulin is effective and devoid of any side effects, it would be a great thing, says Anoop Misra, director and head of the department of diabetes and metabolism, Fortis group of hospitals, New Delhi. “Insulin is actually a growth-promoting hormone and a sudden infusion anywhere else other than blood may trigger a cancerous condition,” he said. “But if it works, it may make a hell of a lot difference to those who currently depend on insulin injections.”
Biocon, with its work at a very advanced stage, is not the only one that is trying to develop an alternative, pain-free route for insulin delivery. Recently, a team of researchers at Syracuse University in New York found that when insulin is attached to a vitamin B-12 molecule, which acts as a carrier, it can be safely transported through the gastrointestinal tract (GIT). This Trojan Horse strategy, in which vitamin B-12 hides the insulin and carries it across the GIT “walls”, also ensures a low and continuous release of insulin.
“Our’s is still in pre-clinical stages whereas Biocon has progressed well into clinical trials,” Syracuse University Assistant Professor Robert Doyle, who led the research, told KnowHow. Interestingly, Doyle has already struck a deal with the Serum Institute of India, Pune, for using this Trojan Horse strategy for developing effective oral vaccines against tetanus and rotavirus infections.
An Indian researcher at the University of Toronto in Canada too is spearheading similar work on oral administration of insulin. Lakshmi Prem Kotra, who has a basic engineering degree from the Birla Institute of Technology and Science in Pilani, told KnowHow that his team is taking a different approach.
The work, which recently appeared in Bioorganic & Medicinal Chemistry Letters, focuses on designing “drug-like” molecules that mimic the effects of insulin on the human body. Towards this, they have developed a very high-resolution atomic model of how the insulin binds to its receptors (areas on the outer part of a cell that allow insulin in the blood to join or bind with the cell). The next step, according to Kotra, is to create molecules that not only bind to the receptor but also activate in a fashion similar to the insulin at this receptor.
“If one is successful in coming up with such molecules, one will not need insulin any more! One can imagine a scenario where a pill taken once a day or once a week is doing the same job as insulin,” Kotra told KnowHow.
Apart from oral means, pharmaceutical companies, are already exploring the inhalation route to deliver insulin in the blood. For instance, Generex Biotechnology, the Toronto-based Canadian firm, has already received approval for Oral-lyn, which is absorbed in the bloodstream through buccal mucosa — the soft tissues lining the inside of the mouth. Oral-lyn is already available in the Indian market.
So diabetics who suffer from an acute form of the disease can soon hope to stay away from needles. As one researcher puts it: oral insulin will certainly be a reality, the question, however, is just when.
Researchers working on an artificial pancreas believe they are just a few years away from a nearly carefree way for people with diabetes to monitor blood and inject insulin as needed.
They believe they can link two current technologies — continuous glucose monitoring and insulin pumps — into a seamless package. Such a mechanical pancrease could greatly reduce the need for fingersticks and injections of insulin that diabetics must now endure several times a day, researchers told a meeting this week at the National Institutes of Health. “I think we are on the brink of a first-generation artificial pancreas,” said Dr Roman Hovorka of Britain’s University of Cambridge, who is testing some experimental devices with components by Abbott Laboratories and Medtronic, the No 1 maker of insulin pumps and continuous monitors.
Hovorka’s team has been testing devices in patients with type-1 diabetes, an autoimmune disease caused when the body mistakenly destroys the insulin-making cells in the pancreas. A continuous glucose sensor is implanted under the skin, and transmits blood sugar readings to a monitor.
A computer calculates the right dose of insulin, which is delivered by an insulin pump — something many patients already wear. His team is ready to send some patients home with the device, but has to work out the logistics of keeping a nurse full-time in each volunteer’s home, just in case. US Food and Drug Administration regulators are working closely with the researchers to ensure they design studies in a way that can lead to quick review, said Dr Aaron Kowalski of the Juvenile Diabetes Research Foundation, which funds many of the artificial pancreas study teams.