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FGF1 Injects Fresh Ideas into Type 2 Diabetes Research

by Jody Barbeau PhD, August 5, 2014 at 08:44 AM | Tags

Type 2 diabetes cannot be cured and is managed by a regimen of exercise, diet, and drugs. As the currently available treatments have a raft of side effects, including weight gain and blood sugar dropping to dangerously low levels, new therapies are needed to control the disease with fewer complications. Some impressive preclinical data were published last month which meet these demands – an FGF1 injection that quickly and effectively lowers blood sugar in diabetic mice with seemingly none of the side effects seen from other antidiabetic agents. Could this be the knockout jab that type 2 diabetes therapies have been looking for?

Type 2 diabetes is a chronic disease where glucose builds up in the bloodstream due to not enough insulin being produced, or due to cells becoming insulin resistant. It is largely the result of excess body weight and inactivity, and as lifestyles become more sedentary and obesity levels increase type 2 diabetes rates have rocketed around the world. Recent figures in the UK showed that more than 700 people per day are diagnosed with type 2 diabetes, with over 300 million people worldwide affected by the disease. There is no cure for type 2 diabetes, instead the disease is managed by diet, exercise, and a range of drugs which aim to increase insulin levels and reverse insulin resistance by changing expression levels of genes. However, the currently available drugs can cause glucose levels to drop too low (leading to life-threatening hypoglycemia) and also have common side-effects including weight gain, nausea, and stomach problems, as well as more serious heart and liver issues. Newly published preclinical research in Nature could be pointing to a new therapy for type 2 diabetes with less side effects involving FGF1.

Fibroblast growth factor 1 (FGF1) is a cellular growth factor and an autocrine/paracrine regulator that has been previously shown to help mice respond to insulin. Mice without FGF1 develop diabetes when given a high fat diet, which led researchers to speculate whether giving FGF1 to diet-induced diabetic mice might help the symptoms of the disease. And that is exactly what happened in the current study with quite spectacular results. A single dose of FGF1 given to diabetic mice was shown to quickly reduce high blood sugar levels back to normal for more than 48 hours, without the drop to dangerously low levels that can be seen with currently available drugs. Instead, the injections restored the body's natural ability to regulate insulin and blood sugar levels, and prolonged use improved insulin sensitivity by about 50%. The injections had the added bonus of not causing any of the other side effects seen with marketed type 2 antidiabetes agents, with no weight gain, heart and liver problems, and no bone loss seen.

The authors of the study would like to move on to human trials of FGF1, and hope that this could lead to a potential new and improved therapy option for type 2 diabetes. While the results and the potential for a trial are very promising there are still a lot of questions to be answered. The mechanism of action of FGF1 still needs to be fully understood, with the signaling pathways and receptors FGF1 interacts with needing to be found. An FGF1 variant would also need to be found that solely affects glucose and does not affect cell growth. It is also important to note that while no side effects were seen in mice, it is very unlikely that a new maintenance therapy option for diabetes would not cause some side effects in humans.

Crown Bioscience welcomes promising preclinical research in the diabetes field, and waits to see what further developments follow on from these impressive findings. Crown Bioscience supports research into diabetes through the use of our clinically relevant in vitro and in vivo models available for translational sciences and drug discovery, including the world’s largest collection of well characterized naturally diabetic NHP models. Contact us today at busdev@crownbio.com to discover how we can transform your diabetes research.


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