Delving into the Latest Updates on RAFT Pharmaceuticals LLC with Synapse

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Nervous System Diseases

Recombinant protein

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Nervous System Diseases	1

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Recombinant protein	1

Author: Catroli, Glaucilene F. ; Durant, Christopher P. ; Xia, Yining ; Ghosheh, Yanal ; Kufareva, Irina ; Agatisa-Boyle, Colin ; Lu, Jenny W. ; Navia-Pelaez, Juliana M. ; Saylor, Benjamin ; Beaton, Graham ; Yaksh, Tony L. ; Miller, Yury I. ; Winkels, Holger ; Corr, Maripat ; dos Santos Aggum Capettini, Luciano ; Kim, Jungsu ; Choi, Soo-Ho ; Gonçalves dos Santos, Gilson ; Gonen, Ayelet ; Ley, Klaus ; Delay, Lauriane

Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1–deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling the TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.

100 Deals associated with RAFT Pharmaceuticals LLC

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100 Translational Medicine associated with RAFT Pharmaceuticals LLC

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Pipeline

Pipeline Snapshot as of 30 Jul 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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