Research into an experimental type 1 diabetes drug has shown that it appears to stop and reverse the condition in mice, and can even prolong their life.
The antibody drug, called mAb43, works by shielding insulin-making beta cells from attacks by the body’s immune system.
With type 1 diabetes, the pancreas does not produce insulin because the body’s own immune system attacks the pancreatic cells that creates insulin. This means that the body is unable to regulate its blood sugar levels.
By using mAb43 to target these cells specifically, it could enable the drug to be used in humans long-term, with limited side effects.
The findings offer hope for the development of a new drug for type 1 diabetes.
mAb43 is a monoclonal antibody, a type of antibody which is made by cloning or replicating an animal cell line, including human cells.
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The promising results have led researchers to set their sights on developing a humanised version of the antibody with a view to carrying out clinical trials to test its ability to prevent type 1 diabetes.
In England, the number of people with type 1 diabetes is more than 270,000, while globally, around 8.4 million people are estimated to have the condition. It is predicted that by 2040, between 13.5 million and 17.4 million people across the world will be diagnosed with type 1 diabetes.
Researcher and postdoctoral fellow Devi Kasinathan, from Johns Hopkins University School of Medicine, 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 glycaemic control.”
mAb43 attaches to a small protein found on the surface of beta cells, which make up clusters called islets. The drug acts as a type of cloak which conceals beta cells from attacks by immune system cells, which treats beta cells as ‘invaders’.
Using a mouse version of the monoclonal antibody, researchers gave a weekly dose of mAb43 to 64 non-obese mice at 10 weeks old which had been bred to develop type 1 diabetes.
All of the mice were non-diabetic by 35 weeks. One mouse did develop the condition for a period but no longer had diabetes by week 35. That particular mouse showed early signs of diabetes before receiving the doses of mAb43.
In five mice which were diabetes-prone, they did not receive mAb43 until they were 14 weeks old. They were then monitored for up to 75 weeks, with continued doses during this time. One of the five went on to develop diabetes but no adverse effects were seen.
Importantly, the mice which were given mAb43 early on lived for the 75-week monitoring period, while mice in the control group, which did not receive any mAb43, lived for between 18-40 weeks.
In the next stage of the study, researchers looked in more detail at the mice which received mAb43 doses. They used a biological marker called Ki67 to monitor if beta cells were reproducing in the pancreas. They found that immune cells backed away from beta cells, leading to a reduction in inflammation in that region. Crucially, beta cells slowly began to multiply.
Another finding was that mAb43 specifically bound to beta cells. Beta cells make up around 1% to 2% of pancreas cells.
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The U.S Food and Drug Administration (FDA) approved another monoclonal antibody drug, teplizumab, in 2022.
Teplizumab is safer for insulin-producing beta cells as it works by binding to T cells. It has been found to delay stage 3 of type 1 diabetes by around 24 months. This allows young children with the condition to mature and gives them more time to learn how to manage dietary changes and insulin injections.
Dax Fu, associate professor of physiology at the Johns Hopkins University School of Medicine and leader of the research team, said: “It’s possible that mAb43 could be used for longer than teplizumab and delay diabetes onset for a much longer time, potentially for as long as it’s administered.
“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.”
Researcher Zheng Guo, a postdoctoral fellow, added: “In an ongoing effort, we aim to develop a humanised 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.”
Read the study in the journal, Diabetes.
