Objective
Type 1 diabetes (T1D) is a condition where the immune system mistakenly attacks the pancreas, destroying insulin-producing beta cells and leading to high blood sugar levels. The objective of this project is to develop a new approach that specifically targets the immune response against beta cells while preserving overall immune function. We will also study how this strategy works to induce tolerance. We will develop specialized whole-body imaging techniques to non-invasively monitor the immune response and track disease progression. This comprehensive approach aims to induce and monitor antigen-specific tolerance in T1D.
Background Rationale
Type 1 diabetes (T1D) is an autoimmune disease where the immune system attacks the pancreas, destroying insulin-producing beta cells. Current treatments focus on immune suppression, which can cause deleterious side effects. This project aims to develop a targeted approach that blocks the immune response against beta cells, while preserving overall immune function. By understanding and monitoring this targeted immune response, we hope to pave the way for better management and treatment options for T1D, to delay its onset and progression.
Description of Project
When the immune system mistakenly attacks the beta cells in the pancreas that produce insulin, it leads to Type 1 diabetes (T1D), characterized by high levels of sugar in the blood. Current treatments involve wholesale suppression of the entire immune system, which can have unwanted side effects, such as an increased risk of opportunistic infections. Here we propose a novel approach that blunts the immune response only against insulin-producing beta cells, while leaving the remainder of the immune system fully functional. We will use nanobodies – small, engineered proteins – to deliver molecules and cells designed to block only the harmful immune response in a mouse model of T1D. We will investigate how these nanobodies work at the molecular level. We will study the genes and molecules involved in the immune response to understand how this treatment affects them to prevent further damage. Next, we will generate the human version of this approach to be tested on human cells implicated in T1D. Lastly, we will develop imaging agents, using engineered nanobodies, to follow the immune response in a living animal by positron emission tomography. This will allow us to track immune cells and see if they respond to treatment. Through a combination of these approaches, we will be better equipped to eliminate the harmful immune response that causes T1D. This could lead to improved treatments with fewer side effects and provide new ways to diagnose and monitor T1D. Our ultimate goal is to develop more effective treatments for T1D.
Anticipated Outcome
The anticipated outcome of this project is the establishment of a novel method that targets the immune response against beta cells in Type 1 diabetes (T1D) while maintaining overall immune function in mouse models of T1D. By understanding the mechanisms behind this targeted approach, as well as the accompanying immune monitoring imaging strategy, we aim to set benchmarks that can be applied to the human setting. This research will help pave the way for clinical applications, to result in better management and treatment of T1D. The novel mechanism we uncover will shed light on how to induce tolerance to specific targets. This will improve our understanding of immune tolerance and open new avenues for other therapeutic strategies.
Relevance to T1D
This research is highly relevant to T1D as it seeks to develop a novel strategy to delay the onset and halt the progression of T1D. It may also help to make beta cell transplantation a viable treatment option. This could lead to improved management and treatment of T1D, offering patients hope for better clinical outcomes and quality of life.