TTP-RA
// TTP-RA
Overview
TTP-RA is an oral, small molecule, antagonist of the receptor for advanced glycation end-products (RAGE) in preclinical development as a potential agent to prevent or delay the onset of type 1 diabetes. In partnership with Professor Josephine Forbes (Mater Research, The University of Queensland, Brisbane, Australia) and Professor Kevan Herold (Yale University, New Haven, USA), and with funding from JDRF (now known as Breakthrough T1D), vTv Therapeutics has investigated RAGE antagonists for this indication.
// TTP-RA
Nonclinical Studies
In nonclinical studies, TTP-RA reduced immune system activity linked to type 1 diabetes and delayed the development of diabetes in mouse models that naturally develop the disease. When TTP-RA was combined with an immune-modulating antibody therapy, it prevented diabetes even in a more aggressive disease model in which immune regulation is impaired.
Mechanism of Action
RAGE is a cell-surface receptor that plays a key role in inflammation and chronic disease. RAGE is expressed on T cells, antigen-presenting cells, and pancreatic beta (β) cells. RAGE ligands are released during β-cell stress, death, or inflammation, and engagement of RAGE can promote T cell activation, survival, and pro-inflammatory cytokine production. In in vitro studies, TTP-RA prevented interactions between RAGE and a broad range of RAGE ligands.