Metformin Therapy for Fanconis Anemia
Abstract
Fanconi anemia (FA) is a devastating genetic bone marrow failure (BMF) syndrome that usually presents in childhood. Most FA patients develop severe progressive anemia, suffer multiple medical complications, and the average life expectancy is less than 40 years. Unfortunately, the drug therapy used for treating FA does not cure the disease and has not changed in over 30 years. Our project is aimed at developing better medications to prevent and treat BMF in this disease. Our laboratory has tested many chemicals in mice genetically engineered to be models of FA. We have recently found that the widely used diabetes drug metformin improves blood counts in FA mice. Metformin is prescribed to millions of people for diabetes and is very safe to use, even in children. However, before this drug can be used in human FA patients, we need to find out more information about several aspects of this new therapy: What is the best dose to prevent BMF in FA? Does metformin work only to prevent BMF, or can it also help when the anemia has already started? Does metformin prevent the deterioration of blood counts associated with acute infections and inflammation? How does metformin interact with the drugs currently used for FA, i.e., anabolic steroids? Can we combine metformin with anabolic steroids and get additional benefit from the combination? We plan to answer all of these questions in mouse models of FA. If the experiments are promising, we believe that a clinical trial of metformin or metformin + anabolic steroid could be started in the near future. Our study is novel in that metformin has never been reported to have any effects on the bone marrow or be beneficial for the treatment of anemia. Currently, no medication is known to prevent/delay bone marrow failure in FA and anemia prevention is a new approach in this disease. Anabolic steroids are used only after the anemia has already started. Our work is highly significant for patients with FA who are waiting for improved therapy, particularly in terms of prevention of BMF. The proposed studies have true translational relevance because metformin is already in clinical use in both adults and children. Hence, the safety profile of the drug is very well established. In addition to the obvious potential impact on FA patient care, this project will yield information about how metformin works at the molecular level. The mechanistic insights we hope to gather could open up new uses of metformin in other forms of BMF.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610300
Entities
People
- Markus Grompe
Organizations
- Oregon Health & Science University
- United States Army