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)
New drug being developed using compound found in red wine ‘could help humans live until they are 150
Drugs that could combat aging and help people to live to 150-years-old may be available within five years, following landmark research.
The new drugs are synthetic versions of resveratrol which is found in red wine and is believed to have an anti-ageing effect as it boosts activity of a protein called SIRT1.
Pharmaceutical giant GlaxoSmithKline has been testing the medications on patients suffering with medical conditions including cancer, diabetes and heart disease.
The work proves that a single anti-ageing enzyme in the body can be targeted, with the potential to prevent age-related diseases and extend lifespans.
As each of the 117 drugs tested work on the single enzyme through a common mechanism, it means that a whole new class of anti-aging drugs is now viable, which could ultimately prevent cancer, Alzheimer’s disease and type 2 diabetes.
Genetics professor David Sinclair, based at Harvard University, said: ‘Ultimately, these drugs would treat one disease, but unlike drugs of today, they would prevent 20 others.
‘In effect, they would slow ageing.’
The target enzyme, SIRT1, is switched on naturally by calorie restriction and exercise, but it can also be enhanced through activators.
The most common naturally-occurring activator is resveratrol, which is found in small quantities in red wine, but synthetic activators with much stronger activity are already being developed.
Although research surrounding resveratrol has been going on for a decade, until now the basic science had been contested.
Despite this, there have already been promising results in some trials with implications for cancer, cardiovascular disease and cardiac failure, type 2 diabetes, Alzheimer’s and Parkinson’s diseases, fatty liver disease, cataracts, osteoporosis, muscle wasting, sleep disorders and inflammatory diseases such as psoriasis, arthritis and colitis.
Professor Sinclair said: ‘In the history of pharmaceuticals, there has never been a drug that tweaks an enzyme to make it run faster.’
The technology was sold to GlaxoSmithKline in 2008.
Four thousand synthetic activators, which are 100 times as potent as a single glass of red wine, have been developed – with the best three being used in human trials.
Writing in the journal Science, Professor Sinclair, who suggests the first therapeutic to be marketed will be for diabetes, said: ‘Our drugs can mimic the benefits of diet and exercise, but there is no impact on weight.’
Limited trials have been carried out in people with type 2 diabetes and the skin inflammatory disease, psoriasis.
Scientists found that there were benefits to the metabolism in the first group and a reduction in skin redness in the second.
The drugs can be administered orally, or topically.
So far, there have been no drugs developed to target ageing skin, but one major skin care range has developed a creme with resveratrol in it.
While any drug would be strictly prescribed for certain conditions, Professor Sinclair suggests that one day, they could be taken orally as a preventative.
They could therefore be used in the same way as statin drugs are commonly prescribed to prevent, instead of simply treating, cardiovascular disease.
In animal models, overweight mice given synthetic resveratrol were able to run twice as far as slim mice and they lived 15 per cent longer.
Professor Sinclair added: ‘Now we are looking at whether there are benefits for those who are already healthy.
‘Things there are also looking promising. We’re finding that aging isn’t the irreversible affliction that we thought it was.
‘Some of us could live to 150, but we won’t get there without more research.’
Attribution: Lucy Crossley, Daily Mail
Millions of diabetes sufferers face the daily grind of frequent and painful skin prick tests to monitor their blood sugar levels.
A team from The University of Akron have developed a contact lens that senses glucose which is the blood sugar in tears, the natural fluid that bathes the eye.
If sugar is not being metabolized properly and glucose concentration builds up in the body, the contact lens will detect a problem and change color.
“It works just like pH paper in your high school chemistry lab”, said Dr Jun Hu.
“The sugar molecule literally acts like the proton in a pH test, displacing a color dye embedded in the lens, and the lens changes color.”
Usually when you dissolve sugars in water you can’t see them. Dr Hu has used a molecule, called a probe, that binds well to sugars that they then combined with a dye. When sugar concentrations rise the sugar binds to the probe and knocks the dye loose, causing a color change.
The person wearing the lens wouldn’t notice the change unless they looked in the mirror, so the team are now designing an app that will calculate sugar levels from a camera phone snap of the eye.
Dr Hu said, “This device could be used to detect subtle changes in blood sugar levels for tight management of diabetes. It can also be used to identify patients with pre-diabetic conditions, allowing early diagnosis that is crucial for preventing diabetes from advancing.”
“The convenience of contact lenses could boost patient compliance to blood sugar testing, as it will reduce discomfort, inconvenience, and even cost.”
“In addition, blood sugar also changes rapidly throughout a normal, active day, so a device that can monitor glucose many times in a day will provide diabetic patients with a very powerful tool in combating such a damaging condition.”
The lens is currently at the prototype phase but scientists say they could be commercially available within three years if all goes well.
The next step will be to check that the dye binds completely to the contact lens and does not leach as this could be dangerous to the eye.
Why do heavy coffee drinkers have a lower risk of developing Type 2 diabetes, a disease on the increase around the world that can lead to serious health problems? Scientists are offering a new solution to that long-standing mystery in an ACS, ‘Journal of Agricultural & Food Chemistry’ report.
Scientists are reporting new evidence that drinking coffee may help prevent diabetes and that caffeine may be the ingredient largely responsible for this effect. Their findings are among the first animal studies to demonstrate this apparent link.
Ling Zheng, Kun Huang and colleagues explain that previous studies show that coffee drinkers are at a lower risk for developing Type 2 diabetes, which accounts for 90-95 percent of diabetes cases in the world.
Those studies show that people who drink four or more cups of coffee daily have a 50 percent lower risk of developing Type 2 diabetes and every additional cup of coffee brings another decrease in risk of almost 7 percent.
Scientists have implicated the misfolding of a substance called human islet amyloid polypeptide (hIAPP)in causing Type 2 diabetes, and some are seeking ways to block that process. Zheng and Huang decided to see if coffee’s beneficial effects might be due to substances that block hIAPP.
Indeed, they did identify two categories of compounds in coffee that significantly inhibited hIAPP. They suggest that this effect explains why coffee drinkers show a lower risk for developing diabetes. “A beneficial effect may thus be expected for a regular coffee drinker”, the researchers conclude.
The scientists fed either water or coffee to a group of laboratory mice commonly used to study diabetes.
Coffee also caused a cascade of other beneficial changes in the fatty liver and inflammatory adipocytokines related to a reduced diabetes risk.
Additional lab studies showed that caffeine may be “one of the most effective anti-diabetic compounds in coffee,” the scientists say.