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With its mission to provide safe and effective treatment options for patients living with cholesterol-driven diseases, Renatus has focused on deriving next-generation cyclodextrins with better safety and better cholesterol-modulating effect compared to the traditional ones.

Based on rational design of chemical structures and engineering technology to produce cyclodextrins as designed, we have discovered new cyclodextrin entities with the desired features. They will allow broad and safe application of cholesterol modulators for various cholesterol-driven diseases.

Lead product : RN-005

RN-005 is a proprietary cyclodextrin developed by Renatus, which is designed to minimize ototoxicity, the major dose-limiting side effect of cyclodextrin, and to improve cellular cholesterol efflux.

RN-005 and its derivatives are being tested in various cholesterol-driven diseases including chronic kidney disease, atherosclerosis, Alzheimer's disease and others.


RN-005 promotes cellular cholesterol efflux


In cells diseased with excessive cholesterol accumulation, RN-005 effectively induces cholesterol efflux, which is about 5 times more potent than HPβCD. Enhancement of cholesterol efflux by RN-005 has been demonstrated in various cell lines. 

Also, significant increase in cellular ABCA1 and cholesteryl ester implies cholesterol metabolism enhanced by RN-005. 


RN-005 prevents plasma membrane disruption 

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Disruption of plasma membrane is known as the main cause of cyclodextrin-induced outer hair cell death and ototoxicity. 

Plasma membrane cholesterol extraction by RN-005 is about 5-times lower than HPβCD. As a result, cytotoxicity and hemolytic activity caused by membrane disruption are significantly low with RN-005.

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RN-005 induces no significant ototoxicity

To study whether reduced cellular membrane disruption leads to protection from hearing loss, RN-005 was injected at a very high dose (8,000 mg/kg) into mice. An auditory brainstem response (ABR) test, a safe and painless test to see how the hearing nerves and brain respond to sounds, shows that RN-005 does not induce any increase in hearing thresholds as opposed to HPβCD. Furthermore, histological analysis confirms no significant loss of outer hair cells after RN-005 treatment as opposed to 40% loss after HPβCD treatment.

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RN-005 exhibits superb systemic safety

RN-005 not only significantly reduces ototoxicity but also shows greater systemic safety as measured by body weight change and behavioral score at a high dose (8,000 mg/kg).

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The preferential removal of intracellular cholesterol over plasma membrane cholesterol by RN-005 will allow its broad and safe application for various cholesterol-associated diseases.

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