Posted by The patent application of Renatus (US2024238327 (A1) ― 2024-07-18) claims for a pharmaceutical composition including a gamma-cyclodextrin-based polymer, for prevention and treatment of diseases related to cholesterol metabolism dysregulation; and use thereof for prevention or treatment of diseases related to cholesterol metabolism dysregulation. The new formulation may minimize extraction of plasma membrane cholesterol and thus not cause cytotoxicity and hemolytic activity, thereby facilitating intracellular metabolism and excretion of cholesterol, and effectively suppressing the secretion of IL-1β, MCP-1, and TNF-α cytokines, thereby exhibiting an excellent anti-inflammatory effect.
Renatus Inc. presented preclinical data from its Alzheimer’s disease program at the 2024 Scale-Up Challenge Lab Conference, held on November 6 in Incheon, South Korea. The presentation covered data from two preclinical models of Alzheimer’s disease using zebrafish and mice, where treatment with Renatus’ proprietary cholesterol modulator, RN-005, consistently led to significant cognitive improvement. Furthermore, systemic administration of RN-005 effectively reduced amyloid-β plaques, neuroinflammation, neuronal cell death, and tau phosphorylation, underscoring the potential of cholesterol modulation to address the complex pathology of AD.
In a mouse model of Alzheimer’s disease, RN-005 induced significant cognitive improvement at a dose where hydroxypropyl-β-cyclodextrin (HPβCD) showed no therapeutic effect at all. RN-005 has a distinct mechanism of cholesterol inclusion compared to HPβCD, which is key to its superior effectiveness at lower doses and safety at higher doses.
While HPβCD removes cholesterol from the cell membrane causing cytotoxicity, ototoxicity, hemolysis, the gamma-CD polymer (RN-005) removes selectively the harmful cholesterol while preserving healthy levels of cholesterol where needed.
Despite its superior ability to bind with free cholesterol, RN-005 is designed to not to interact with cholesterol within the plasma membrane.