Objective
We will determine the safety and efficacy of a drug used to treat psoriasis, bimekizumab, in decreasing the fraction of diabetogenic islet antigen specific T cells in young adults with new onset T1D at 6 months and 1 year of treatment. We will determine if this drug slows or prevents beta cell loss in individuals who have recently been diagnosed with T1D and if the administration of the drug results in better control of blood sugars in these individuals.
Background Rationale
Previous studies in individuals with T1D have shown that types of immune cells called Th17 cells and Th1 cells work to destroy insulin producing beta cells. Our recent studies with a drug that blocks the activation of these two cell types have shown that this drug, called ustekinumab, is safe and can delay the loss of insulin producing islet cells at one year. However, this drug must be given for over more than 6 months to see a clinical effect. We propose that potent blocking of Th17 cells with a drug, bimekizumab, that blocks the IL-17 chemical, will result in more rapid inhibition of these potentially damaging cells, and more rapid clinical effect.
Description of Project
In type 1 diabetes (T1D), cells from the immune system called T cells attack and destroy insulin-producing beta cells leaving affected individuals with a lifelong dependence on insulin. Even with insulin injections, blood glucose control is imperfect, leading to an increased risk of complications from chronic hyperglycemia and a shortened life span. We demonstrated that a biologic drug (an antibody known as ustekinumab) that inhibits inflammation can be safely administered to young adults with new onset T1D. In adolescents with T1D, this drug inhibits the loss of islets, but only after 6 months or treatment. This effect is associated with an inhibition of a subset of immune cells called Th17 cells. Ustekinumab blocks these cells indirectly by blocking chemicals that are required for these cells to survive (termed IL-12 and IL-23).
We propose a pilot trial to test the ability of bimekizumab, a drug that more rapidly and potently blocks Th17 cells, by blocking the chemical IL-17 directly, to halt the progression of T1D in adults with recent- onset T1D. 30 young adults with new onset (within 100 days of being diagnosed) T1D will be randomly assigned to receive the drug for 6 months, or 1 year, or a placebo for 1 year and changes in the fraction and number of islet damaging cells as well as the progression of damage to the pancreas will then be followed. We believe that if IL-17 can be blocked soon after the development of diabetes, then the remaining insulin-producing cells in the pancreas may be protected, and regenerate. We will assess the ability of the drug to block the activity of the harmful immune cells that produce inflammatory cytokines and damage the islets, and to decrease their number. Overall, our proposal will test the safety and efficacy of using bimekizumab to improve the outcomes for individuals with recent onset T1D. We will also examine the utility of using changes in the number and fraction of Th17 cells as a biomarker (clinical test) of our ability to block the progression of diabetes.
Anticipated Outcome
We anticipate that doses of bimekizumab used for the treatment of adults with psoriasis, psoriatic arthritis, and ankylosing spondylitis, will be safe in individuals with new onset T1D. We also believe that bimekizumab will prevent the activation and number of islet-harming T cells by 6 months of treatment, and possibly reduce the need for insulin and preserve endogenous insulin secretion. This study will inform the design of subsequent clinical trials of bimekizumab for the treatment of new onset T1D and will inform the design of other studies using biomarkers tested in this work.
Relevance to T1D
This project is highly relevant to T1D as it tests a potential drug therapy (bimekizumab) that may preserve beta cell function and insulin secretion. Further, a primary aim is to determine if changes in the fraction of Th17 cells and islet antigen specific Th17 cells can be used as biomarkers to assess inhibition of beta cell destruction.