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One of the most common chronic disease in children and adolescents is type 1 diabetes; studies reveal that more than 40 million individuals are affected worldwide by the condition. In patients with type 1 diabetes, the pancreas no longer produces insulin because the body’s immune system attacks its beta cells for reasons still unknown. Today’s primary treatments are insulin therapy and some diet modifications, and people with T1D require multiple injections every day to control their blood sugar levels.
The first action to generating more successful T1D treatments is to identify the causes of the disease; that is to say, any real progress towards a true cure for diabetes type 1 will necessarily involve beta cell replacement either by pancreas or islet transplantation. These promising alternatives to daily injections will restore the possibility of controlling glucose levels and produce insulin accordingly.
Scientists at Washington University in St Louis, Missouri, have reported exciting news in the development of particular methods to turn stem cells into pancreatic beta cells, and now, they have combined these techniques with the CRISPR gene-editing tool to reverse diabetes in mice.
One of the methods used to replenish these stocks of pancreatic beta cells is by making them out of human stem cells that can mature into almost any type of cell in the human body.
The research goal was to employ CRISPR to correct genetic defects leading to diabetes, and the resulting ‘edited’ beta cells combined with the stem cell therapy would produce even more effective results.
The scientists took skin cells from a patient with a rare genetic type of diabetes called Wolfram syndrome, which develops during childhood and typically involves multiple insulin injections each day. These skin cells were converted into induced pluripotent stem cells, which were in turn converted into insulin-secreting beta cells. But as an additional step, CRISPR was used to correct a genetic mutation that causes Wolfram syndrome.
These edited beta cells were then pitted against non-edited beta cells from the same batch in test tube experiments and in mice with a severe type of diabetes. The edited cells proved more efficient at secreting insulin, and when implanted under the skin in mice, reportedly caused diabetes to quickly disappear. The rodents that received the unedited beta cells remained diabetic.
“This is the first time CRISPR has been used to fix a patient’s diabetes-causing genetic defect and successfully reverse diabetes,” said co-senior investigator Jeffrey R. Millman.
The project brought together outstanding expertise from The Washington University researchers who have also made other huge strides, most recently with a cell implantation method that “functionally cured” mice with diabetes.
Scientists are now working on improving the beta cell production techniques, allowing cells taken from the blood or urine, rather than the skin, in the future.
This study built a path towards what has the potential to be a real discovery towards a cure for type 1 and type 2 diabetes, by correcting mutations and defects that result from genetic and environmental factors that cause or contribute to the disease, opening doors to treat other medical conditions.
“We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation,” said co-senior investigator Fumihiko Urano.
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The research was published in the journal Science Translational Medicine.
Source: Washington University
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