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Progress has been made towards a potential solution to type 1 diabetes. The novel approach seeks to cure type 1 diabetes and to allow type 2 diabetics to stop using insulin shots by altering other cells in the pancreas so they produce insulin.

The research team based at UT Health San Antonio have found a way to increase the types of pancreatic cells that secrete insulin. The team are now moving towards starting clinical trials in the next three years, but they are first testing the approach in larger-sized animals. These studies are believed to cost an estimated $5 million.

These studies will pave the way for an application to the FDA for Investigational New Drug (IND) approval, which will hopefully see the new therapy moving into clinical trials and ultimately to the people who need it.

Cured diabetes in mice

The preclinical results thus far have been promising and the strategy has cured diabetic mice of the disease.

Dr. Doiron, assistant professor of medicine at UT Health, said: “We cured mice for one year without any side effects. That’s never been seen. But it’s a mouse model, so caution is needed. We want to bring this to large animals that are closer to humans in physiology of the endocrine system.” – source

Ralph DeFronzo, M.D., professor of medicine and chief of the Division of Diabetes at UT Health describes the therapy “The pancreas has many other cell types besides beta cells, and our approach is to alter these cells so that they start to secrete insulin, but only in response to glucose [sugar],” he said. “This is basically just like beta cells.” – source

This means that even if the beta cells are not producing insulin, the other pancreatic cells can take up the slack and keep the metabolism going. Essentially, the other cells function just like beta cells.

What is insulin?

Insulin works by reducing blood sugar levels but it is only made by beta cells. In type 1 diabetes beta cells are attacked and destroyed by the immune system, so the person cannot produce insulin; in type 2 diabetes, beta cells fail and insulin levels decrease. Also, the body does not use insulin efficiently with type 2 diabetes.

Diabetes is also of interest to LEAF as it relates directly with aging and deregulated nutrient sensing as described in the hallmarks of aging[1]. In some ways, diabetes might be considered accelerated aging of tissue, as it indeed speeds up the aging process in affected tissues.

A therapy that is able to encourage other cell types is therefore a novel and exciting approach to bringing this disease under control.

Making other cells produce insulin

This new therapy uses gene transfer, where a viral vector (or carrier) is used to introduce new genes into cells in the pancreas. These new genes then integrate into the cells allowing them to produce insulin in response to the presence of glucose, just like beta cells normally do.

Gene transfers using viral vectors has been used globally to treat an array of diseases. It has already proven effective in treating rare childhood diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy.

In type 1 diabetes, the body rejects the beta cells and the immune system attacks them, but in this new approach the other cell populations in the pancreas remain unharmed by the immune system even when they have received the therapy. This means they could potentially produce insulin as needed without being attacked, and restore normal metabolic function to those with diabetes.

Precise control of blood sugar

The new therapy gave second-by-second regulation of blood sugar levels in the mice, just like in healthy non diabetic mice. If this approach could be translated to humans, it would be a considerable improvement over regular insulin therapy or medications that can cause blood sugar to fall too low if not monitored carefully.

A major problem in the field of type 1 diabetes is hypoglycemia, where blood sugar falls dangerously low. The gene transfer therapy the researchers are proposing is potentially groundbreaking, as the altered cells perform the same function as the beta cells and only release insulin in response to the presence of glucose.

“People don’t have symptoms of diabetes until they have lost at least 80 percent of their beta cells” Dr. Doiron said.”We don’t need to replicate all of the insulin-making function of beta cells,” he said. “Only 20 percent restoration of this capacity is sufficient for a cure of Type 1.” – source

This would suggest that, if a therapy can restore just 20% insulin production capacity, then it might be enough to cure diabetes.

Conclusion

As with all preclinical research and results in mice, we should be cautious here until further studies are concluded. There are various hurdles to overcome getting through clinical trials, so we should be positive but mindful of the challenges.

With that said, the idea of repurposing cells in our body is gaining traction in the research world, as we saw recently with a similar approach with Parkinson’s, where researchers reprogrammed cells in the brain to change from one type to another to replace lost dopamine-producing neurons. Whilst the researchers in this experiment used cellular reprogramming and this study used gene therapy, the ideas are similar.

The kinds of therapies now being developed in the labs will make current medicine seem primitive in the next decade or two. How we treat age-related diseases is poised to change dramatically in the near future with a shift to repair and prevention over simply coping with and treating symptoms.

Hopefully, that day will arrive sooner rather than later and, we will be able to wave goodbye to diseases like diabetes thanks to new technologies and approaches in medicine. We wish Drs. Doiron and DeFronzo the best of luck for their research and hope that the journey to clinical trials will be swift and successful.

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

CategoryBlog, Research
About the author

Steve Hill

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
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