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Genetics and CRISPR take aim at diabetes identification and treatment

Study: Use CRISPR to place edited cells in diabetic mice
Genetics and CRISPR take aim at diabetes identification and treatment hero image

Diabetes affects at least 285 million people worldwide and can cause everything from unquenchable thirst to heart disease, stroke, and kidney damage.

The exact cause is unknown, but genes and lifestyles likely play a role. Now, genetics is stepping in to both find the reasons behind its occurrence and offer solutions.

In July, a study in Cell Host & Microbe by a team of German researchers used high-throughput 16S RNA gene sequencing to profile microbial community composition in fecal samples of nearly 2,000 Germans enrolled.

The work found identifiable levels of specific bugs varied throughout the day, and particularly among individuals with Type 2 diabetes or who were obese. The findings, the authors wrote, suggest “a functional link between circadian rhythms and the microbiome in metabolic diseases.”

The disease can be signaled by arrhythmic bacteria, noted Genetic Engineering & Biotechnology News.

“Certain gut bacteria do not follow a day-night rhythm, so if their number and function do not change over the course of the day, this can be an indicator for a potential type 2 diabetes disease,” one study co-author stated. “Knowing this can improve diagnosis and outlook of type 2 diabetes.”

Meanwhile, another new study, this one published this spring in Science Translational Medicine, highlights the potential that CRISPR-led gene therapy could correct stem cells from diabetic patients and turn them into fully functioning beta cells.

This work piggybacks off an experiment conducted in the 1990s that transplanted insulin-producing cells from the recently deceased into Type 1 diabetes patients, the results of which offered a temporary respite from insulin injections.

The new CRISPR effort placed edited cells in mice with diabetes, and after doing so researchers found that blood sugar in the mice normalized. The authors think the method could be used to treat humans with Type 1 and Type 2 diabetes.

“After transplanting the corrected beta cells into diabetic mice, the animals saw their blood glucose drop quickly, suggesting the disease had been reversed,” noted Fierce Biotech. “The effect lasted for the entire six-month observation period, the scientists reported. By comparison, those receiving unedited cells from patients were unable to achieve glycemic control.”

This experiment avoided ethical concerns surrounding the use of human embryonic stem cells in gene therapy by instead subbing in a patient’s own cells, noted Jeffrey Millman, the study’s co-senior author, in a video statement, and that also eliminates the risk of potentially harmful gene edits going into cells in the body.

“Now we can generate a virtually unlimited number of beta cells from patients with diabetes to test and discover new drugs to hopefully stop or even reverse this disease,” he stated.

If successful, the new method could introduce a radical new way to treat the disease.

"In the future," co-senior investigator Fumihiko Urano told Science Daily, "we may be able to take a few milliliters of urine from a patient, make stem cells that we then can grow into beta cells, correct mutations in those cells with CRISPR, transplant them back into the patient, and cure their diabetes in our clinic. Genetic testing in patients with diabetes will guide us to identify genes that should be corrected, which will lead to a personalized regenerative gene therapy." 

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