In today’s health-centric world, one common worry associated with consuming excess sugar is the threat of diabetes. However, this narrative only accounts for the more infamous type of diabetes, Type 2, which affects hundreds of millions of people worldwide. Patients with Type 2 diabetes maintain a functional pancreas; however, it becomes resistant to insulin, a hormone responsible for controlling the levels of sugar within our blood. This process occurs overtime, primarily due to excess weight. Insulin regulates sugar levels and allows sugar to be stored in the liver. Without it, sugars accumulate in our blood, leading to dire health implications such as heart problems, nerve damage, and pregnancy complications. The lesser known sibling of Type 2, Type 1, is a chronic condition in which the pancreas makes little to no insulin. In Type 1 diabetic patients, the immune system mistakenly identifies pancreatic beta cells, which are responsible for producing insulin, as foreign invaders and attacks them. Most cases are genetic, with a majority of Type 1 patients experiencing symptoms in adolescence. Daily insulin injections or an insulin pump are essential for managing Type 1 diabetes, as the body cannot produce insulin naturally. Only 5-10% of individuals with diabetes have Type 1, making it substantially less common. However, it still affects millions of individuals worldwide who constantly have to stress about their sugar levels. To target this, researchers are focusing on understanding autoimmune triggers to potentially develop preventative treatments. Advancements in medicine, such as immunotherapy, are offering new hope for managing or even curing Type 1 diabetes.
For scientists researching Type 1 diabetes, the immune system has always been under constant scrutiny. If scientists are able to identify why or how beta cells are being flagged as foreign by the immune system and are subsequently attacked, then a drug can be engineered to avoid them. Thus, understanding and controlling the immune system would be immensely beneficial in treating Type 1 diabetes. Recent innovations in medicine and technology have enabled scientists and doctors worldwide to make headway in this field, with several drugs emerging as frontrunners in the fight against diabetes. One such drug, mAb43, may prove to be the answer scientists have been looking for.
In Type 1 diabetes, an immune cell called T lymphocytes attacks islets, or bundles of beta cells. Devi Kasinathan, a researcher at Johns Hopkins, and her team research islets and their interactions with lymphocytes. They developed mAb43, a drug that protects islets from T lymphocytes, subsequently preserving the beta cells and allowing for insulin secretion. The drug works as a shield, latching onto the Zinc Transporter 8 (ZnT8) protein abundantly present on the surface of the islets and preventing the lymphocytes from recognizing the cells, hence inhibiting lymphocyte attack. While the effects of this drug are remarkable, the exact immunological mechanisms that enable the drug to mask the beta cells from T lymphocytes remains unclear.
To progress a drug and make it available for treatment, mice and human trials must be conducted and approved by the FDA. Currently, their drug has made its way through early phases of mice trials and have shown promising results. The researchers at Johns Hopkins administered the drug in 5 mg/kg doses weekly to the mice starting at 10 weeks of age, along with a control group that did not receive any dose. All mice were already genetically predisposed to Type 1 diabetes since they were immunodeficient, or unable to fight off infectious diseases. Results showed that mAb43 successfully masked beta cells, and all of the mice given mAb43 maintained normal amounts of glucose in their blood, also known as euglycemia. None of these mice developed diabetes as opposed to the controls. Furthermore, in a study analyzing the delayed effect of the drug, four out of every five experimental mice were found to maintain euglycemia until 40 weeks of age, a remarkable percentage considering that all mice in the control group for this study developed diabetes. The researchers then discontinued the treatment in some mice at different ages and found that when off the treatment, all the mice eventually developed diabetes. The mice that continued to be treated, however, never developed diabetes and demonstrated significantly higher amounts of beta cells than the control. With such promising results, the drug will hopefully enter human clinical trials to see if the impact in mice translates to humans.
Johns Hopkins University is not the only research institute paving the way for revolutionary treatments. Researchers at the University of Miami have developed a unique treatment that focuses on replacing the dead beta cells with new ones via pluripotent stem cells, which are cells that have not yet differentiated into specialized cells. This approach significantly differs from the mAb43 drug;rather than preserving beta cell mass within patients, this treatment aims to restore mass by generating entirely new beta cells. The treatment incorporates a revolutionary immunomodulatory microgel, iTOL-100, which allows for the body to accept transplanted islets without the need for immunosuppression, a process that uses medication to disable the immune system to ensure the patient’s body does not reject the transplant. Paired with IsletRx, which are human, stem cell-derived islets, patients can reverse the damage caused by Type 1 diabetes and maintain a functioning pancreas.
Mount Sinai is another leader in developing groundbreaking treatments from Type 1 diabetes. Rather than regenerating beta cells with a transplant, researchers instead combine a natural plant product called harmine with GLP1 receptor agonists, which are substances that bind to GLP1 receptors and elicit the same reaction as insulin would. After transplanting human beta cells into mice with no immune system, they found that the harmine-GLP1 treatment rapidly reversed both types of diabetes and even allowed for a 700% increase in beta cell counts. This treatment is the first drug treatment to increase human beta cell counts in vivo, or in living organisms, creating a new milestone for diabetes treatment. Currently, the drug has completed phase one of human clinical trials with promising results.
Unfortunately, there are few, if any, preventive measures that can be taken to avoid the onset of Type 1 diabetes, as the condition is primarily driven by genetic factors. However, once diagnosed, there are effective ways to manage the disease and mitigate its symptoms. Yale Medicine emphasizes the importance of lifestyle changes, such as maintaining a healthy diet and regular exercise, as well as closely monitoring blood glucose levels and adhering to prescribed insulin therapy. These actions can help manage the condition, reduce the risk of complications, and improve overall quality of life for those living with Type 1 diabetes. Continued research from institutions like Johns Hopkins, UMiami, and Mt Sinai are bringing scientists one step closer to finding a permanent solution for Type 1 diabetes.
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