Scientists at Johns Hopkins Medicine have discovered an experimental monoclonal antibody drug called mAb43 that appears to prevent and reverse the onset of clinical type 1 diabetes in mice, potentially lengthening their lifespan. This drug is unique as it targets insulin-making beta cells in the pancreas directly and shields them from attacks by the body’s own immune system cells. The researchers believe that this drug may have minimal side effects in humans due to its specificity for beta cells. Monoclonal antibodies are created by cloning animal cell lines to make identical replicas.
Type 1 diabetes is an autoimmune condition where the immune system attacks pancreatic cells that produce insulin, leading to a lack of insulin production and difficulty regulating blood sugar levels. Current treatment for type 1 diabetes involves lifelong insulin injections and can result in various complications if not managed properly. The study, led by Dax Fu, Ph.D., of Johns Hopkins University School of Medicine, found that mAb43 binds to a protein on the surface of beta cells, providing a shield to hide them from immune system attacks. The researchers used a mouse version of the antibody and will need to develop a humanized version for future studies in humans.
In the animal study, mice that received weekly doses of mAb43 starting at 10 weeks of age remained non-diabetic after 35 weeks. Even mice that initially developed diabetes recovered after 35 weeks of treatment. A second group of mice that started receiving mAb43 at 14 weeks of age also had a reduced incidence of diabetes, with no adverse events reported. The treated mice lived longer compared to a control group that did not receive the drug, suggesting a potential lifespan extension with mAb43 treatment.
Further analysis of the treated mice showed that mAb43 reduced inflammation in the pancreas by causing immune cells to retreat from beta cells, allowing beta cells to slowly regenerate. The researchers used a biological marker called Ki67 to confirm the proliferation of beta cells in the pancreas after treatment with mAb43. This regeneration of beta cells could potentially reduce the need for insulin supplementation in combination with mAb43 therapy, offering a promising approach for managing type 1 diabetes.
The research team also compared mAb43 to another monoclonal antibody drug called teplizumab, which was approved by the FDA in 2022. Teplizumab targets T cells to protect insulin-producing beta cells and delays the onset of type 1 diabetes by approximately two years. The researchers believe that mAb43 has the potential to delay diabetes onset for a longer duration, potentially as long as it is administered. Future plans include developing a humanized version of the antibody for clinical trials to evaluate its efficacy in preventing type 1 diabetes and any potential off-target side effects.
Overall, the findings from this study highlight the potential of mAb43 as a novel treatment for type 1 diabetes by targeting beta cells in the pancreas. The specificity of the antibody for beta cells and its ability to shield them from immune attacks offer a promising therapeutic approach for managing and potentially preventing the development of type 1 diabetes. Through continued research and clinical trials, scientists hope to further evaluate the safety and efficacy of mAb43 in humans and potentially provide a new treatment option for individuals with type 1 diabetes.
