Objective
We aim to use a combination of animal models and human samples to clearly test if LRRK2 inhibitors can prevent beta cell demise and arm the beta cell with a way to survive immune attack.
Background Rationale
Currently, there are no available drugs to strengthen beta cells in the prevention or during the active development of T1D. Using a class of drugs never envisioned for T1D before, we hope to rapidly expand testing in model systems and allow the beta cell a way to cope to immune attack. Together with exciting new drugs targeting the immune system (teplizumab), we believe beta cell targeting will be a valuable partner to ongoing immune therapies for diabetes. LRRK2 inhibitors improve the health of mitochondria (the power plant of the cell). We know that mitochondria are sick in beta cells in T1D and there is enough energy available for beta cells to survive. Therefore, targeting beta cell mitochondria could provide the cell the energy necessary to respond to immune attack.
Description of Project
The goal of this proposal is to determine if a class of safe and well tolerated drugs currently used in clinical trials for Parkinsons disease can be used to help beta cells survive immune attack in type 1 diabetes.
Anticipated Outcome
We expect that LRRK2 drugs will prevent or hasten diabetes in mouse models and improve beta cell health in cultured human islet beta cells. We also predict these drugs will improve mitochondria and the energy production needed for beta cells to survive. With use of pre-clinical mouse data and human samples, we are poised to await FDA approval for LRRK2 drugs for Parkinsons disease, hopefully allowing for future studies with these drugs to treat or prevent T1D.
Relevance to T1D
This study directly targets beta cells in the development of T1D. We know insulin is not a cure and preventing or regenerating beta cells that are lost are absolutely vital. In this study, we use new and safe drugs to improve beta cell health and ideally prevent or hasten T1D development.