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Scientists at Yale University have devised a particularly promising new drug to combat type 1 diabetes: not only does it help regulate blood sugar, but it is able to restore pancreatic function and restore “normal” immune function in the pancreatic environment. Successfully tested in mice, this drug could revolutionize the treatment of diabetes, and its “mode of action” appears to be a promising new approach for the treatment of other autoimmune diseases.
Type 1 diabetes is an autoimmune disease caused by a dysfunction of the T lymphocytes: the latter identify the beta cells of the pancreas – which synthesize and secrete insulin – as foreign cells to the body and therefore eliminate them. Therefore, the disease is characterized by insufficient or no insulin production, which leads to a prolonged increase in the concentration of glucose in the blood (so-called hyperglycemia); in normal times, insulin converts glucose into energy.
Type 1 diabetes accounts for around 10% of diabetes cases in France and worldwide. Treatment is based on an exogenous insulin supply, in the form of subcutaneous injections, several times a day. The drug developed by the Yale researchers is not only more convenient (as it can be taken orally), but it can also reverse the inflammatory effects of the disease. “This is a two-pronged approach. This facilitates normal metabolism and corrects long-term immune defects, ”says Tarek Fahmy, associate professor of biomedical engineering and immunobiology, who led the research.
A new approach to the administration of oral insulin
For people with diabetes, swallowing an insulin pill would be a much more convenient and less invasive routine than daily injections. The problem is that in this way, insulin is necessarily destroyed in the gastrointestinal system before it reaches the bloodstream, where it is believed to regulate glucose levels. Therefore, many scientists are trying to develop a method that allows insulin to resist the acidic gastric juice of the stomach, with the aim of improving its intestinal absorption and increasing its bioavailability in the blood.
For example, a team at MIT has designed a capsule with a microneedle, which injects insulin into the bloodstream through the lining of the stomach. Researchers at the University of Niagara in the United States have developed a new encapsulation method, based on patented particles known as cholestosomes; These lipid molecules, which are not vulnerable to stomach acids, are used to produce insulin-containing vesicles. Other scientists at New York University, Abu Dhabi, have developed “smart” nanoparticles: once in the blood, these insulin-loaded nanoparticles automatically control the patient’s insulin level and do not release hormones into the blood only when necessary.
The polymerized form of ursodeoxycholic acid increases its ability to bind to receptors on cells in the pancreas, helping to restore normal metabolism in the short term and restore immune function in the long term. © J. Seok Lee et al.
Professor Fahmy’s team has also developed a new “transport medium” for drugs based on nanoparticles, which protect insulin while transporting it to the pancreas where it can discharge its precious contents. These nanoparticles are composed of ursodeoxycholic acid, a bile acid produced naturally in the body, which the researchers polymerized. In its most natural form, as a monomer, it has already been used to make drugs intended to dissolve gallstones and liver stones. However, in this way it has not been shown to be very effective as a treatment for diabetes.
One pickup for two effects
By polymerizing this acid, Fahmy’s team was able to increase its ability to bind to receptors on pancreatic cells, improving metabolic functions and, more importantly, reducing unwanted immune cells that destroy beta cells. In other words, the insulin “vehicle” itself has therapeutic effects, helping to restore normal metabolism in the short term and to restore immune function in the long term. “We cure the disease by maintaining insulin levels. […] This combined approach is what makes this system a promising new therapy for autoimmune diseases in general ”, emphasizes the specialist.
These nanoparticles made of polymerized ursodeoxycholic acid restored blood glucose levels in mice and pigs with type 1 diabetes. They improved insulin levels in animals, reduced inflammation and restored metabolic function. The team also found that the insulin delivered by these oral capsules worked roughly seven times faster than that delivered by standard subcutaneous injection. Furthermore, encapsulation of rapamycin (an immunosuppressant) by the same method made it possible to delay the onset of diabetes in mice with chemically-induced pancreatic inflammation, the researchers note.
The results are quite promising, but more work will be needed to determine if they are reproducible in humans. This mode of drug delivery not only has enormous potential for diabetes, but also for other diseases. “I am optimistic that this technique will be used to develop urgent solutions to today’s difficult challenges in terms of autoimmunity, cancer, allergies and infections,” concludes the researcher.
Nature Biomedical Engineering, J. Seok Lee et al.
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