Development of Nongenotoxic Hematopoietic Stem Cell Transplantation Regimens for Fanconi Anemia
Abstract
Bone marrow transplantation has been used for decades to treat and cure patients suffering from many types of blood or immune diseases, with more than one million patients treated to date. This therapy is one of the only effective, long-lasting treatments for bone marrow failure (BMF) conditions such as Fanconi anemia (FA). Bone marrow transplantation relies on replacing sick blood-forming stem cells in patients with healthy ones from a donor, resulting in a completely new blood and immune system. However, this process currently requires use of irradiation and/or chemotherapy, which can be extremely harmful, especially to FA patients whose cells cannot fix DNA mistakes caused by these agents. We think we can make this procedure safe and eliminate all of the bad side effects through the use of proteins called antibodies that can attach to specific parts on the outside of cells, including the diseased blood-forming stem cells in the bone marrow of BMF patients. Once attached, these antibodies will induce safe elimination of the diseased bone marrow. When the blood-forming stem cells are removed, we can replace them with healthy donor cells. This type of therapy could be used to treat blood problems in BMF patients, but also prevent them all together if used upfront in recently diagnosed patients or patients known to have BMF predispositions such as those caused by genetic mutations. Here, we aim to test if the antibody treatment safely and efficiently eliminates the defective cells in FA mouse models, as well as test if a similar human-equivalent antibody can effectively enable blood and immune system turnover post bone marrow transplantation. This work could improve our scientific understanding of the blood forming stem cells in FA disease, but moreover could lead to the development of fully safe, effective as easy transplant protocols that could be used in FA as well as in other diseased settings, which could benefit thousands of patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110262
Entities
People
- Agnieszka Czechowicz
Organizations
- Stanford University
- United States Army