“Participating in the program is an adventure that most young scientists don’t know. To be able to meet donors directly who put their trust and faith in you and your work, gives you a concrete reason to invest your efforts in a project in which people trust and see the positive impact that it could bring to help tomorrow’s patient.”
“It’s very hard to go from an idea to something concrete. The Tullie and Rickey Families SPARK Program builds the golden bridge for your idea, to bring it directly where it can grow in the best conditions.”
Can we cure autoimmune diseases with a single therapy?
FUNDED: JANUARY 2021
FUNDED BY: the generosity of The Rosemary Kraemer Raitt FoundationTrust, John and Cim Kraemer and 2020 Various Donors
Autoimmune diseases such as psoriasis, scleroderma, multiple sclerosis, diabetes or immune disorders such as allergies are due to a misguided or disproportionate immune reaction. Autoimmune disorders are sharply on the rise in modern society particularly affecting women. Available treatments consist of daily or emergency medications. Therefore, I propose a novel approach that re-edits the immune cells involved in the autoimmune reaction, targeting autoimmune diseases at their root.
The main culprit in most autoimmune disease are autoreactive T cells, which recognize and destroy cells in the body. T cells are generated and educated in the thymus, a small organ in front of the heart, before they travel throughout the body. Our goal is to prevent autoreactive T cells from leaving the thymus.
Recently, it has been shown that a subset of immune cells, so called plasmacytoid dendritic cells (pDCs), are able, under certain conditions, to migrate to the thymus and trigger the death of the autoreactive T cells. They are doing so by capturing and displaying fragments of tissue proteins on their surface. When these “loaded” dendritic cells travel to the thymus and they trigger the self-destruction of any immune cells that recognize that particular tissue protein, thus eliminating autoreactive T cells.
The purpose of this project is to mimic this physiological elimination process by generating pDC that express tissue proteins and can find their way to the thymus in a mouse model of type 1 diabetes. In mice just as in humans with type 1 diabetes, autoreactive T cells recognize insulin and destroy the cells that produce it. In healthy people, trace amounts of insulin are present in the thymus helping to build a natural immune tolerance of insulin. I will inject modified pDCs that carry insulin into the thymus of NOD mice, which spontaneously develop type 1 diabetes, to build this immune tolerance and prevent the development of diabetes.
Six-Month Project Update
It may be possible to generate therapeutic cells to treat many types of autoimmune diseases. For my SPARK project, I tested the techniques and technology we’ll need to develop the best therapeutic cells. It shows that cells from bone marrow can differentiate into dendritic-like cells and migrate to the thymus, the organ where T cells develop. This discovery shows us that bone marrow cells can express the right molecular tools to let them migrate through the body—even after they are modified in the laboratory. Our follow-up research in a mouse model confirmed that cells expressing this protein, called CCR9, prefer to migrate to the thymus.
Thanks to this work, we now have the tools in place to analyze and track these modified cells. The next step is to confirm that the migration of those cells in the thymus can prevent or cure autoimmune disorders. The first model of autoimmune disorder will be the type I diabetes in mice. We hope this gives us a window into treating type 1 diabetes and the mystery of how that disease develops in the first place.
Hear from 2020 SPARK finalists Dr. Annie Elong Ngono, Mehdi Benkahla, Ph.D., and Simon Brunel, Ph.D. as they share their gratitude for your support and reflections on the transformative impacts of SPARK on medical research solutions, and the careers and lives of the young scientists behind those solutions.