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A Less Controversial Application For Gene Editing: Obesity And Diabetes

This technique may one day improve our lives and potentially help us to correct and possibly cure diseases.
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Over the last week, gene editing has been getting quite a bit of attention, although most of it has been negative. The reason stems from a research study in which the technique was used to correct a genetic mutation in embryos. Concerns over designer babies were raised and heated arguments over the ethics of the technique quickly arose.

At the heart of the debate is a technique known as CRISPR-Cas9. It originally was found in bacteria as a means to prevent infection from viruses, known as bacteriophages. But over the last few years, researchers have managed to find a way to develop this phenomenon for use in animal and human cells.

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Although the embryo modification paper puts CRISPR-Cas9 in a rather difficult place in terms of public acceptance, the concept of gene editing can be seen as a very good thing for our future. Despite the negative reactions to this one study, others are showing how this technique may one day improve our lives and potentially help us to correct and possibly cure diseases.

One such study was published by an American team of researchers. Their focus dealt with two very common diseases, obesity and diabetes. Their use of gene editing was far less controversial and based on the results, could open up an avenue for a new type of chronic disease therapy using not drugs but an individual's own cells.

The researchers focused on a small hormone known as Glucagon-like Peptide 1, shortened to GLP-1. Despite its small size, it is a major player in metabolism as it helps to control our appetite and also the release of insulin in the body. This is especially important for those suffering from weight management problems as well as diabetes. Previous clinical trials have shown the addition of this molecule can help people suffering from both Type 1 and Type 2 diabetes. The molecule is so important, several pharmaceutical treatments for diabetes attempt to act like GLP-1 in the body.

While this in itself was remarkable, the true goal of this study was yet to be tested.

For this recent study, the aim was to determine if genetic editing could help the body produce higher concentrations of GLP-1 on its own. But going inside the body would be far too invasive and most likely never progress past the lab-based studies. They believed there was a safer way with the potential to be used in real-life situations. Instead of blood or internal organs, they focused on the skin.

Skin grafts are a common procedure and known to be quite safe. For the researchers, grafting one's own cells would be a sure way to accomplish their goal. All they needed to do was ensure they could engineer skin cells to produce GLP-1.

The group chose two different types of cells to test whether engineering would work. The first came from newborn mice to prove they could accomplish this task in an animal model. The other cells came from human foreskin, which could show the potential for use of this technique in humans.

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The first stage involved using CRISPR-Cas9 to edit the genetic material in these cells. The focus was on increasing the production of GLP-1 such that these cells became mini-factories of the hormone. As they expected, the results were a success as the newly engineered cells pumped out the hormone.

With this in place, the team worked with mice to determine if skin grafts could accomplish their goal. The first test involved a mouse-to-mouse transplantation. As expected, the procedure was successful and the GLP-1 levels in the body rose. The same occurred with mice capable of receiving human transplants.

But while this in itself was remarkable, the true goal of this study was yet to be tested. The team wanted to show the technique could have lasting effects on the body. They wanted to show the grafts could lead to positive changes in GLP-1 concentration, body weight and risk for diabetes.

The use of human cells reveals this path for treatment could be explored in the human context.

Over the course of 10 weeks, mice that had undergone the surgery as well as those who had not were given a rather heavy diet consisting of high fats. Normally, this would lead to overeating, weight gain, obesity and diabetes. However, in the mice who had received the grafts, the massive weight gain did not happen. Their appetites were controlled and their ability to use glucose did not change. The researchers had achieved their goal by using a skin graft to prevent these conditions. The authors had achieved the results they desired.

This study reveals the potential power for gene editing in therapeutics of chronic disease. Although mice were the only recipients, the use of human cells reveals this path for treatment could be explored in the human context. While this won't happen for quite some time, this study reveals CRISPR-Cas9 may be one option to improve the chances for appropriate therapy of obesity and diabetes.

More importantly, this study highlights how using gene editing under the right circumstances can be both effective and ethical. The use of cells rather than embryos certainly will reduce concerns in the general public. Also, skin grafts are far less worrisome than other surgically invasive procedures. Granted, this route may not be the first choice for therapy should it be developed and accepted. Yet, the potential for an effective option with relatively little to no side effects is enticing particularly to those who unsuccessfully have tried the usual pharmaceutical routes. It may even pave the way for gene editing to receive cheers rather than what happened last week, which for the most part, was jeers.

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