Potential Targeted Therapy for Type I Diabetes: Monoclonal Antibodies

Type 1 diabetes, known as T1D, is characterized by an autoimmune response where harmful lymphocytes attack autoantigens found in the pancreatic islets, resulting in the loss of insulin-producing beta cells in the pancreas. The absence of insulin hinders the body's capacity to control the levels of glucose in the bloodstream. It impacts approximately 2 million American children and adults with no known cure or preventive measures (1^✔ ✔Trusted Source
Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice

Go to source). This differs from type 2 diabetes, in which the pancreas produces insufficient insulin.

A report has been published recently in the May issue of diabetes, by the scientists at Johns Hopkins Medicine, on a new experimental drug that could be a potential targeted therapy for type 1 diabetes. The experimental drug is a monoclonal antibody named mAb43. It has the potential to stop and reverse the development of clinical type 1 diabetes in mice, and in certain instances, extend the lifespan of the animals.

The researchers claim that the drug possesses a distinctive quality as it directly focuses on the insulin-producing beta cells in the pancreas. Moreover, it is specifically designed to protect these cells from the body's immune system cells (2^✔ ✔Trusted Source
Experimental Type 1 Diabetes Drug Shelters Pancreas Cells from Immune System Attack

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According to the researchers, this unique characteristic of the drug allows for its long-term usage in humans with minimal adverse effects. These monoclonal are produced through cloning, which involves creating identical copies of an animal or human cell line.

How Does the New Experimental Drug Help?

Dax Fu, Ph.D., associate professor of physiology at the Johns Hopkins University School of Medicine and leader of the research team, said, “People with type 1 diabetes face lifelong injections of insulin and many complications, including stroke and eyesight problems if the condition is not managed properly,”.

Fu explains that mAb43 specifically attaches to a protein located on the outer layer of beta cells, which are organized in groups known as islets. This drug aims to create a protective barrier for beta cells, shielding them from immune system cells that perceive them as foreign entities. In their experiments, the scientists utilized the monoclonal antibody derived from the mice, but further research will be required to produce a humanized version suitable for human studies.

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The study assessed the prolonged effectiveness and safety of multiple doses of mAb43 in NOD (non-obese diabetic) mice (3^✔ ✔Trusted Source
Diabetes

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Study Details

In the study design, a group of 64 non-obese mice specifically bred to develop type 1 diabetes, were administered a weekly dosage of mAb43 through intravenous injection starting at the age of 10 weeks. Following a period of 35 weeks, all mice exhibited non-diabetic conditions. In particular, one of the mice experienced diabetes temporarily, but it successfully recovered at the 35-week mark. It is worth mentioning that this particular mouse displayed early indications of diabetes prior to the administration of the antibody.

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In the control group, the researchers refrained from administering weekly mAb43 doses to five mice susceptible to diabetes until they reached 14 weeks of age. Subsequently, they proceeded with the dosages and closely monitored the mice for 75 weeks. Out of the five mice, only one developed diabetes, and no negative incidents were observed, as reported by the researchers.

Data generated in the study showed that in the trials where mAb43 was administered at an early stage, the mice survived throughout the entire 75-week monitoring period. However, in the control group of mice who did not receive the medication, the mice had a lifespan of approximately 18-40 weeks.

Subsequently, the scientists, along with postdoctoral fellows Devi Kasinathan and Zheng Guo, conducted a detailed examination of the mice treated with mAb43. They made use of a biological marker called Ki67 to assess whether beta cells were undergoing multiplication in the pancreas. Following the antibody treatment, it was noted that immune cells receded from the beta cells, resulting in a reduction of inflammation in the vicinity. Moreover, beta cells started gradually replicating.

Kasinathan said, “mAb43 in combination with insulin therapy may have the potential to gradually reduce insulin use while beta cells regenerate, ultimately eliminating the need to use insulin supplementation for glycemic control,”.

The team of researchers discovered that mAb43 exhibited a specific affinity towards beta cells, which constitute approximately 1% or 2% of the pancreatic cell population.

In 2022, teplizumab, a different monoclonal antibody medication, was approved by the US FDA. It attaches to T cells, reducing harm to insulin-producing beta cells and delaying the onset of stage 3 type 1 diabetes by about two years. This gives young children time to adjust to lifelong insulin injections and dietary limitations.

Fu mentioned it is possible that mAb43 may have a longer duration of use compared to teplizumab, leading to a delay in the onset of diabetes for an extended period, possibly for the entire duration of its administration.

Guo concluded, “In an ongoing effort, we aim to develop a humanized version of the antibody and conduct clinical trials to test its ability to prevent type 1 diabetes, and to learn whether it has any off-target side effects,”.

This pioneering study shows the promising potential of a novel medication to transform the management of diabetes and enhance the well-being of individuals impacted by the condition.

References:

1. Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice - (https://diabetesjournals.org/diabetes/article/73/5/806/154280/Cell-Surface-ZnT8-Antibody-Prevents-and-Reverses)
2. Experimental Type 1 Diabetes Drug Shelters Pancreas Cells from Immune System Attack - (https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/04/experimental-type-1-diabetes-drug-shelters-pancreas-cells-from-immune-system-attack)
3. Diabetes - (https://www.who.int/news-room/fact-sheets/detail/diabetes)

Source-Medindia