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RN-005
What is RN-005?
RN-005 is a proprietary cyclodextrin developed by RENATUS, which can be manufactured with a simple and scalable synthesis method. It is designed to minimize ototoxicity, the major dose-limiting side effect of cyclodextrin, and to improve cellular cholesterol efflux.
RN-005 prevents plasma membrane disruption
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.
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.
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).
RN-005 improves 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.
Significant increase in cellular ABCA1 and cholesteryl ester implies cholesterol metabolism enhanced by RN-005.
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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