Gene Therapy

FA gene therapy The International FA Gene Therapy Working Group

Fanconi anemia (FA) is caused by defects in any one of 23 different genes. If we could somehow repair or replace these defective genes, we could treat or prevent FA disease. Gene therapy is an approach to do just this. Gene therapy addresses the root cause of inherited diseases like FA by enabling cells to express a copy of a normal FA gene, thus allowing them to produce proteins necessary for health. If we can fix the defect in stem cells, then all blood cells that are derived from a stem cell are also fixed. This should restore normal function to diseased stem cells and prevent bone marrow failure (BMF). FA commonly presents first with BMF, so fixing bone marrow cells to prevent this failure is crucial.

The current standard of care for BMF for people with FA is bone marrow transplant using hematopoietic stem cells from healthy donors. Thanks to advancements in transplant protocols, there is now a 90% chance of survival. Despite this relative success, however, transplants require the use of highly toxic chemotherapy regimens and in some instances total body irradiation to deplete failing FA stem cells before patients can receive healthy donor stem cells. These toxic regimens lead to whole-body DNA damage and increase the risk for the development of graft-versus-host disease (GvHD) and squamous cell cancers in an already at-risk population. That’s where gene therapy comes in.

Current FA gene therapy clinical trials

FARF-funded gene therapy projects

FARF-funded gene editing projects