Back to Our Technologies

TGFβ Inhibition as a Therapeutic Strategy to Prevent Bone Marrow Failure in Fanconi Anemia Patients

Potential new non-invasive therapy to delay the onset or treat bone marrow failure (BMF) in patients with Fanconi Anemia (FA) patients, such as those where HSPC transplantation is not possible.

  • Therapeutics

Project Overview

  • The mechanism of bone marrow failure (BMF) in Fanconi Anemia (FA) remains elusive, and there is a need for a better understanding of the mechanism of BMF in FA as well as improved therapies to treat BMF other than the invasive bone marrow transplant. 
  • Scientists at Dana-Farber have discovered that TGFβ inhibitors improve survival of bone marrow cells.
  • This technology is available for non-exclusive licensing.

Technology

Fanconi Anemia (FA) is a rare autosomal recessive DNA repair disorder characterized by congenital abnormalities, cancer predisposition, and progressive bone marrow failure (BMF). FA patients typically develop progressive BMF during childhood.

Hematopoietic stem and progenitor cells (HSPCs) in FA Patients have lost their ability to detect and repair damaged DNA resulting in the HSPCs accumulating DNA damage and ultimately losing their inability to survive.

Currently, the only curative strategy for blood defects, including BMF, in FA patients relies on an invasive allogeneic, or unrelated matching donor, bone marrow transplantation. Success of this procedure is not guaranteed and outcomes depend on multiple factors. Hence, there remains an unmet need for new therapeutic strategies against FA and the resulting BMF. 

Even though the mechanism of bone marrow failure in FA remains elusive, the labs of Dr. D’Andrea at Dana-Farber made the important discovery that the elevated expression of TGFβ ligand isoforms accounts, at least in part, for BMF in FA patients. Studies showed that inhibition of TGFβ isoforms promote cell proliferation and/or clonogenic survival in a large number of FA patient samples. Hence, inhibition of the TGFβ signaling pathway will restore the growth of human bone marrow cells. The therapeutic potential of TGFβ Inhibition has also been supported by multiple in vivo mouse studies.

Altogether, this shows the promising therapeutic potential of TGFβ inhibitors as a new and non-invasive therapeutic strategy to address BMF in FA patients. 

Team Members: Alan D. D’Andrea, MD, Kalindi Parmar, PhD, Hao-Jian Zhang, PhD

Applications

  • Potential new non-invasive therapy to delay the onset or treat BMF in FA patients especially for those where HSPC transplantation is not an option
  • A new method for the in-vitro expansion of HSPCs 

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these methods for internal research use, or to accompany FA treatment options. 

This asset is available for non-exclusive licensing. 

Get in touch

Team Members