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Using Gene Editing as a Potential Type 1 Diabetes Treatment

It has been more than a decade since scientists began experimenting with CRISPR gene-editing technology to alter DNA sequences and gene function. This tool allows scientists to correct mutations or defects in genes and manipulate them to treat or prevent certain diseases. This technology has also been used with crops. Researchers are still exploring this tool’s potential and ethical use, but many studies have been conducted thus far using it in different ways.

A recent study examines the use of CRISPR-Cas9 in the treatment of diabetes. Scientists at Washington University in St. Louis corrected a mutation in the WFS1 gene which causes Wolfram syndrome, of which diabetes is one symptom. Then, they used CRISPR-Cas9 to edit human-induced pluripotent stem cells and target their differentiation into pancreatic beta cells. This creates an abundance of fully functional beta cells to be used in conjunction with gene therapy.

When the altered beta cells were transplanted into diabetic mice, blood glucose levels dropped and glycemic control was maintained for at least six months. Scientists are exploring whether this process can be used to effectively reverse or stop type 1 diabetes by editing a patient’s own beta cells. In addition, the abundance of cells created means that more testing can occur to develop specific medications or therapies to treat the disease.

More research is needed before gene editing can potentially be used as an approved treatment for type 1 diabetes, but researchers continue to learn more. Diabetes Research Connection (DRC) is interested to see what this technology may mean for the future of diabetes treatment and management and how it could evolve. Though not involved with this study, the DRC is committed to supporting research around type 1 diabetes and provides early-career scientists with critical funding for novel, peer-reviewed studies. To learn more about current projects and how to help, visit https://diabetesresearchconnection.org.

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Recapping Current Research Regarding Type 1 Diabetes Development and Cardiovascular Risks

Our bodies are formed from an innumerable number of cells and molecules. Both DNA and RNA play a role in determining cells’ function and purpose. At a conference of the National Congress of the Spanish Diabetes Society, researchers revealed new studies regarding the potential role of long non-coding RNAs (lncRNAs) in the development of type 1 diabetes, as well as the risk of cardiovascular problems in individuals with the disease.

A recent study found that lncRNA, which are use in transcriptional and post-transcriptional regulation of cells and are not translated into proteins, may be involved in the destruction of insulin-producing beta cells. There may be some forms of lncRNAs that affect inflammation and cell death, which are factors in the development of type 1 diabetes.

Dr. Izortze Santín Gómez, a professor at the University of the Basque Country and a researcher at the Biocruces Bizkaia Research Institute is studying the fundamental characteristics of the lncRNAs and how they may affect pancreatic beta cells on a genetic-molecular level. Once this is better understood, researchers could begin modifying the lncRNAs to create a targeted therapy that increases survival rate and viability of the pancreatic beta cells.

Another study that was presented at the conference involved cardiovascular risk for individuals with type 1 diabetes. Joseph Ribalta, a professor at the Rovira i Vigili University of Reus, found that “more than 30% of heart attacks occur in people with apparently normal LDL cholesterol.” High cholesterol is a key risk factor for heart attacks. His findings have revealed that individuals with T1D may be at greater risk because “LDL particles are more numerous and smaller, that their HDLs work less effectively and/or that there are some lipoproteins (remnants) that the body has trouble eliminating.”

Identifying these potential risk factors and knowing how to test for or treat them could help reduce hidden cardiovascular risk in individuals with T1D. For instance, focusing on triglycerides rather than cholesterol may be beneficial for patients who meet certain criteria.

There is a lot of interesting work coming out of laboratories and universities around the world regarding type 1 diabetes. Researchers are constantly improving and refining their understanding of the disease and possible ways to prevent, treat, or cure it. Diabetes Research Connection (DRC) is committed to contributing to this wealth of knowledge by providing critical funding to early-career scientists pursuing novel research studies focused on type 1 diabetes. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

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Type 1 Diabetes Vaccine Shows Positive Results

In an effort to prevent or delay the onset of type 1 diabetes, researchers have been striving to create an effective vaccine. One of the challenges is that there are many different subgroups of type 1 diabetes, meaning not all patients respond the same. A recent study found that patients who had a specific human leukocyte antigen (HLA) showed a “positive and statistically significant dose-dependent treatment response” to the Diamyd vaccine, especially when given four doses rather than two.

Compared to patients who received a placebo, those who received a higher number of doses of the Diamyd vaccine had a “statistically significant treatment effect of approximately 60%” within 15 months. These findings may help to advance the development of antigen-specific immunotherapy options for individuals with type 1 diabetes leading to improved treatment or management of the disease.

Diabetes Research Connection (DRC) is interested to see how this vaccine continues to evolve moving forward and what it could mean for the prevention of type 1 diabetes in the future. Though not involved with this study, the DRC provides early career scientists with funding necessary to conduct novel, peer-reviewed research projects around type 1 diabetes in an effort to improve understanding, prevention, treatment, and management of the disease. To learn more or donate to a current project, visit https://diabetesresearchconnection.org.

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Improved Protection for Transplanted Stem Cell-Derived Islets

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

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Exploring Why the Immune System May Attack Insulin-Producing Beta Cells

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

Learn More +

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