Transglutaminase 2 (TG2) is a multifunctional protein with enzymatic, cell signaling, and cell adhesion activities. The enzymatic activity of TG2 is believed to contribute to the pathogenesis of a variety of diseases including celiac disease, neurological disorders including Huntington’s Disease, type 2 diabetes, liver cirrhosis and fibrosis, renal scarring, vascular remodeling and several cancers (Siegel and Khosla) (Esposito, Caputo et al.) (Bakker).
TGs have been implicated in the pathogenesis of several neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s Disease, where TG is believed to play a role in protein aggregation and cross-linking. At least eight neurodegenerative diseases including Huntington’s, are caused by (CAG)n expansions in the genome and by an expansion of the corresponding polyglutamine domain within the expressed mutated protein.
Alvine Pharmaceuticals’ portfolio of compounds has promising properties suitable for drug development, and Alvine is in the process of systematically analyzing this portfolio with the objective of advancing compounds from discovery phase into development phase.