Small Molecules for the Treatment of Graft versus Host Disease

Application

Administration of indole derivatives for the treatment of graft versus host disease.

Key Benefits

  • Decreases incidence of GvHD after allogeneic transplantation.
  • Does not create immuno-suppression in recipient.

Market Summary

Graft versus host disease (GvHD) can arise following allogeneic transplantation, which is used for the treatment of diseases that damage bone marrow such as non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, leukemia, multiple myeloma, and aplastic anemia. The current treatment for GvHD is pharmacological immuno-suppression as a prophylactic, which limits the incidence and severity of GvHD but increases the risk of opportunistic infections and relapse.

Technical Summary

Indole-3-dioxygenase (IDO) is the enzyme responsible for the metabolism of the essential amino acid tryptophan. IDO has been implicated in regulating immune responses post transplantation suggesting that the substrates of indole metabolism play a role in the regulation of tolerance and GvHD. Previous studies demonstrated survival after a nonlethal dose of donor T cells was significantly worse in a mouse model lacking IDO than control. Emory Researchers have identified small molecules that are well tolerated in humans as components of certain foods, and appear to play a protective role by affecting IDO and the tolerance system. These molecules confer 90% survival and induce immune tolerance in a murine model of GvHD in which all untreated animals succumb. Protection was also observed in other murine models of autoimmunity including experimental autoimmune encephalomyelopathy (EAE) and radiation enteritis.

Development Stage

Testing of molecules in a murine model for allo-hematopoietic stem cell transplants.

Patent Information

App Type Country Serial No. Patent No. File Date Issued Date Patent Status
Utility (parent) United States 15/268,577 10,154,989 9/17/2016 12/18/2018 Issued
Tech ID: 13197
Published: 6/7/2017