Renatus Inc., a pharmaceutical company developing cholesterol modulators to address dysregulated cholesterol homeostasis observed in various diseases, 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.

“These results provide insight into the significant relationship between cholesterol metabolism and Alzheimer’s disease, adding to a growing body of evidence that highlights impaired cholesterol homeostasis in Alzheimer’s disease patients,” said Heegon Kim, PhD, Chief Executive Officer at Renatus.

He continued, “These findings not only demonstrate the ability of RN-005 to modulate cholesterol metabolism in the brain but also show its significant impact on key cellular pathways involved in the pathogenesis and progression of AD. We believe cholesterol modulators have great potential as disease-modifying drugs for the treatment 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.”

“Cholesterol can lead to health issues, especially as we age. However, targeting cholesterol as a therapeutic approach is challenging because it is everywhere in the body and essential for many functions. It’s crucial to address excess cholesterol selectively without disrupting its necessary roles. Renatus is revolutionizing the field by selectively targeting harmful cholesterol while preserving healthy levels where needed.”

About Alzheimer’s disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions worldwide, leading to cognitive decline, memory loss, and functional impairment. While the precise cause of AD remains elusive, growing evidence highlights a profound association between cholesterol metabolism and the disease's development and progression. The strongest genetic risk factor for late-onset AD is the presence of the ApoE4 allele, a variant of the apolipoprotein E gene involved in lipid transport and cholesterol metabolism. ApoE4 is known to disrupt cholesterol balance in the brain, creating an environment conducive to neurodegenerative changes. This link underscores the critical role of cholesterol pathways in AD pathology, suggesting that modulating cholesterol metabolism could be a promising strategy for combating the disease.

About hydroxypropyl-beta-cyclodextrin (HPβCD)

HPβCD is a modified form of beta-cyclodextrin that can effectively dissolve cholesterol molecules by encapsulating them within the hydrophobic cavity of its ring structure. Preclinical studies have demonstrated that HPβCD has the potential to modulate cholesterol in vivo by promoting its transport and efflux, leading to positive therapeutic outcomes in various neurodegenerative disease models including Alzheimer’s disease and Niemann-Pick Type C. HPβCD is under clinical trials for Alzheimer’s disease and Niemann-Pick Type C1.

About Renatus

Renatus is a pharma company thriving to develop the next generation cyclodextrins to provide safe treatment options for patients living with cholesterol-associated diseases. Renatus seeks to provide critical impact in developing translational cyclodextrin therapies and fulfill its vision to protect the world from various cholesterol-associate diseases. For more information, please visit www.renatustx.com.