Currently, the best treatments for type 2 diabetes involve managing blood sugar levels, but recent research suggests that the brain may be a new drug target for longer-term control. Now, a pair of studies on rats and mice has investigated how a certain peptide works to induce remission for animals with diabetes, which could lead to new breakthroughs in human treatments.
For a few years now, scientists at Washington University have been working on techniques to turn stem cells into pancreatic beta cells as a way of addressing insulin shortages in diabetics. After some promising recent strides, the team is now reporting another exciting breakthrough, combining this technique with the CRISPR gene-editing tool to reverse the disease in mice.
No matter what the latest fad diet tells us to do, we already know the general gist of how to stay healthy – eating too much sugar and fat leads to weight gain and metabolic diseases. But what if you could stay healthier without changing your diet? In mouse tests conducted at the Max Planck Institute for Metabolism Research, researchers have now found a way to alter the fat metabolism in the liver, reducing the chances of diabetes without changing a high-fat diet.
Our bodies store fat in adipose tissue, but after eating high amounts of the stuff over a long period of time it begins to build up in more important places like the liver. That in turn can lead to fatty liver disease, which can then reduce the body’s response to insulin and eventually bring on type 2 diabetes.
A group of fats known as ceramides have long been associated with these metabolic diseases, and plenty of research has in the past focused on lowering their levels by blocking the proteins that create them – ceramide synthases. Unfortunately, it hasn’t always gone to plan.
“Other research groups have already shown that blocking ceramide production in mice prevents the development of insulin resistance,” says Philipp Hammerschmidt, first author of the new study. “However, this is associated with a large number of side effects. If, for example, ceramide synthesis is completely inhibited it can adversely affect the development of the animals.”
For decades researchers have worked to find a way to orally administer insulin effectively to patients with diabetes. Now this game-changing treatment is one step closer to reality, with pharmaceutical company Oramed embarking on a final Phase 2b human clinical trial to prove the efficacy of its oral insulin before moving to the final stages of trials and registrations that could bring the treatment to market within a few short years.
According to the Center for Disease Control, 1.25 million people suffer from type 1 diabetes in the US alone. So far, it can only be managed with diet and regular doses of insulin, but scientists at UT Health San Antonio have invented a way of curing the disease in mice that may one day do the same for humans even with type 2 diabetes.
An ultra-sensitive wristband may improve diagnosis and treatment of cystic fibrosis, diabetes and other conditions, researchers said on Monday.
Unlike previous sweat sensors, the new model requires only a trace of moisture to do its job and doesn’t require patients to sit still for 30 minutes while it collects a sample.
The device contains flexible sensors and microprocessors that stick to the skin and stimulate sweat glands.
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Using stem cells to create insulin-producing beta cells that could be transplanted into diabetics is being investigated as a possible cure for type 1 diabetes and treatment for type 2, but new research suggests that a special diet could reprogram cells in the pancreas to do the same thing.
Introducing a ‘glucose sensor’ by gene therapy eliminates the symptoms of the disease
Researchers from the Universitat Autònoma de Barcelona (UAB), led by Fàtima Bosch, have shown for the first time that it is possible to cure diabetes in large animals with a single session of gene therapy. As published this week in Diabetes, the principal journal for research on the disease, after a single gene therapy session, the dogs recover their health and no longer show symptoms of the disease. In some cases, monitoring continued for over four years, with no recurrence of symptoms.
The therapy is minimally invasive. It consists of a single session of various injections in the animal’s rear legs using simple needles that are commonly used in cosmetic treatments. These injections introduce gene therapy vectors, with a dual objective: to express the insulin gene, on the one hand, and that of glucokinase, on the other. Glucokinase is an enzyme that regulates the uptake of glucose from the blood. When both genes act simultaneously they function as a “glucose sensor”, which automatically regulates the uptake of glucose from the blood, thus reducing diabetic hyperglycemia (the excess of blood sugar associated with the disease).
As Fàtima Bosch, the head researcher, points out, “this study is the first to demonstrate a long-term cure for diabetes in a large animal model using gene therapy.”
This same research group had already tested this type of therapy on mice, but the excellent results obtained for the first time with large animals lays the foundations for the clinical translation of this gene therapy approach to veterinary medicine and eventually to diabetic patients.
The study was led by the head of the UAB’s Centre for Animal Biotechnology and Gene Therapy (CBATEG) Fàtima Bosch, and involved the Department of Biochemistry and Molecular Biology of the UAB, the Department of Medicine and Animal Surgery of the UAB, the Faculty of Veterinary Science of the UAB, the Department of Animal Health and Anatomy of the UAB, the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), the Children’s Hospital of Philadelphia (USA) and the Howard Hughes Medical Institute of Philadelphia (USA).
A safe and efficacious gene therapy
The study provides ample data showing the safety of gene therapy mediated by adeno-associated vectors (AAV) in diabetic dogs. The therapy has proved to be safe and efficacious: it is based on the transfer of two genes to the muscle of adult animals using a new generation of very safe vectors known as adeno-associated vectors. These vectors, derived from non-pathogenic viruses, are widely used in gene therapy and have been successful in treating several diseases.
In fact, the first gene therapy medicine ever approved by the European Medicines Agency, named Glybera®, makes use of adeno-associated vectors to treat a metabolic disease caused by a deficiency of lipoprotein lipase and the resulting accumulation of triglycerides in the blood.
Long-term control of the disease
Dogs treated with a single administration of gene therapy showed good glucose control at all times, both when fasting and when fed, improving on that of dogs given daily insulin injections, and with no episodes of hypoglycemia, even after exercise. Furthermore, the dogs treated with adeno-associated vectors improved their body weight and had not developed secondary complications four years after the treatment.
The study is the first to report optimal long-term control of diabetes in large animals. This had never before been achieved with any other innovative therapies for diabetes. The study is also the first to report that a single administration of genes to diabetic dogs is able to maintain normoglycemia over the long term (more than 4 years). As well as achieving normoglycemia, the dogs had normal levels of glycosylated proteins and developed no secondary complications of diabetes after more than 4 years with the disease.
Application in diabetic patients
There have been multiple clinical trials in which AAV vectors have been introduced into skeletal muscle, so the strategy reported in this study is feasible for clinical translation. Future safety and efficacy studies will provide the bases for initiating a clinical veterinary trial of diabetes treatment for companion animals, which will supply key information for eventual trials with humans. In conclusion, this study paves the way for the clinical translation of this approach to gene therapy to veterinary medicine, and eventually to diabetic patients.
Diabetes mellitus is the most common metabolic disease, and a large number of patients need insulin treatment to survive. In spite of the use of insulin injections to control the disease, these patients often develop serious secondary complications like blindness, kidney damage or amputation of limbs. Moreover, in order to achieve good blood glucose control, insulin has to be injected two or three times a day, which brings a risk of hypoglycemia episodes (lowering of blood sugar): an additional problem that comes on top of the other hardships of the treatment.
Attribution: Real Clear Science (02-07-2013)