Current therapy for FA is limited to allogeneic stem cell transplantation (SCT), a process associated with significant morbidity and mortality, particularly when an ideally matched donor is not readily available. Therefore, novel therapies that improve or replace SCT are needed. Progress in FA thera…
By virtue of their inability to repair a specific form of DNA damage, persons with Fanconi Anemia (FA) are appreciably more susceptible to development of certain cancers. Oral squamous cell carcinoma (OSCC), which arises from the lining cells of the mouth, occurs at >500 fold higher incidence in ind…
The objective of this proposal is to conduct a pilot study of metformin to treat FA. This pilot study will explore whether Metformin is safe and efficacious in improving hematopoiesis in patients with Fanconi Anemia. We will focus on pediatric and young adult patients with FA to determine safety, to…
Fanconi anemia (FA) patients suffer from progressive bone marrow failure due to the defective hematopoietic stem cells (HSCs) in their bone marrow. The mechanisms of why the HSCs in FA patients are defective remain elusive. Recent studies suggest that DNA damage induced by physiological stress or al…
The cause of injury and loss of blood-forming stem cells (Hematopoietic Stem Cells, HSC) in Fanconi anemia is due to abnormal repair of a specific type of DNA damage in which two DNA strands get permanently knotted to each other. This type of injury probably occurs frequently but is normally repaire…
As a monogenic blood disorder with potential survival disadvantage, Fanconi anemia has long been considered an attractive target for conventional gene therapy but success has been elusive. Consequently, there has been increasing interest in developing techniques to catalyze correction of the disease…
This is a training grant for a medical geneticist from Mexico City, who will develop a registry and subsequently a cohort of patients with FA who reside in Mexico. The project addresses one of the research priorities of the FARF:
Fanconi anemia increases the risk of cancer as individuals' age. This is likely due to defects in the Fanconi DNA repair pathway that lead to the formation of rare cancer-causing mutations. Fanconi anemia individuals are defective in both copies of a Fanconi gene (one from mom and one from dad) and …
Fanconi anemia is caused by mutations in number of genes involved in DNA repair. Two key players are genes called FANCD2 and FANCI. These genes serve as central regulators of the Fanconi DNA repair pathway. Dr. Deans and others have shown that regulation occurs through the addition or removal of a m…
In the field of rare diseases it is extremely difficult to perform clinical trials with new chemical entities without prior information on bioavailability, dose and safety in humans. Drug repurposing is the application of known drugs and compounds to new indications. Thus, the aim of this project is…
It has long been recognized that gene-environment interactions influence the clinical course of individuals with FA, yet the underlying mechanisms remain elusive. Drawing on this labs deep expertise in protein folding diseases this project proposes a pragmatic approach to address this issue which ca…
Many have proposed that lentiviral vector (LV)-mediated hematopoietic stem cell (HSC) gene therapy may constitute a new safe and efficient approach for the treatment/prevention of the bone marrow failure (BMF) characteristic of FA patients. To further improve the possibilities of developing a safe a…