Triggering receptor expressed on myeloid cells receptor family modulators: a patent review. (December 2014)

• Record Type: Journal Article
• Authors: Pelham, Christopher J; Pandya, Amit N; Agrawal, Devendra K
• Is Part Of: Expert opinion on therapeutic patents. Volume 24:Number 12(2014:Dec.)
• Page Start: 1383
• Page End: 1395
• Publication Date: 2014-12
• Subjects: Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1517/13543776.2014.977865
• Languages: English
• ISSNs: 1354-3776

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Triggering receptor expressed on myeloid cells (TREM) receptors and TREM-like transcript (TLT; or TREML) receptors of the immunoglobulin superfamily are known as key modulators of host immune responses. TREM-1 (CD354) and TREM-2 share the transmembrane adaptor DNAX-activation protein of 12 kDa (DAP12), but they possess separate stimulatory and inhibitory functional roles, especially in myeloid cells.</p> <p> <bold> <italic>Areas covered:</italic> </bold> This review covers findings related to TREMs and TLTs published in patent applications from their discovery in 2000 to the present. New roles for TREM-1, TREM-2, TLT-1 and TLT-2 in maladies ranging from acute and chronic inflammatory disorders to cardiovascular diseases and cancers are discussed. Putative endogenous ligands and novel synthetic peptide blockers are also discussed.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> So far, therapeutic use of activators/blockers specific for TREMs and TLTs has been limited to preclinical animal models. TREM-1 is an immediate therapeutic target for acute and chronic inflammatory conditions, especially sepsis. Certain mutations in DAP12 and TREM-2 manifest into a disorder named polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and newly identified TREM-2 variants confer a significant increase in risk of developing Alzheimer's disease. This makes TREM-2 an attractive therapeutic target for neurodegenerative diseases.</p> </abstract>