Date: 2015-05-15
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in the Journal of Controlled Release
Company: Celsion (USA - NJ)
Product: inhibitor of microRNA-145 (miR-145) delivered by TheraSilence™ technology platform
Action
mechanism: microRNA. TheraSilence™ is a technology platform for the delivery of synthetically-generated messenger RNA, inhibitory RNA (RNAi) such as small inhibitory RNAs (siRNAs), microRNAs, microRNA mimics, microRNA inhibitors and related molecules that can regulate protein expression at the transcript level by exploiting endogenous cell mechanisms. Inhibitory RNA based therapies have potential for targeting virtually any disease related gene with a high degree of specificity and thus eliminating so called \"non-drugable\" target classes. The technology addresses the primary obstacle to nucleic acid-based therapeutics, which is the safe and efficient delivery to target cells. Celsion\'s proprietary, novel structures are able to interact with the RNAi molecules forming protective nanoparticles that can be readily taken up into cells. In addition, these systems are chemically flexible and amenable to attachment of tissue-targeted ligands, in vivo stabilizing agents and other functional moieties which can tailor a formulation for a particular application and delivery modality. These features can provide high specificity for RNAi delivery to select tissue, enhance stability and reduce in vivo toxicity.
Disease: pulmonary arterial hypertension
Therapeutic area: Rare diseases - Cardiovascular diseases
Country:
Trial details:
Latest
news: * On May 15, 2015, Celsion reported the publication of an abstract in the Journal of Controlled Release summarizing findings from a preclinical study confirming effective delivery of RNA to lung cells. In the study, the Company\'s TheraSilence™ technology platform safely and effectively delivered an inhibitor of microRNA-145 (miR-145) in a well-established model of severe occlusive pulmonary arterial hypertension (PAH). Increased expression of miR-145 has been linked to the development and progression of PAH in humans. Treatment was associated with significant delivery of miR-145 inhibitor in the lung, inhibition of miR-145 levels and reversal of the pulmonary hypertension associated with the advanced stages of the disease leading to a normalization of cardiovascular function. This preclinical program was conducted in collaboration with Dr. William Gerthoffer at the University of South Alabama. Celsion\'s TheraSilence™ RNA delivery platform is designed to enable the preferential delivery to the lungs of synthetically-generated mRNA, inhibitory RNA (RNAi) such as small inhibitory RNAs (siRNAs), microRNAs, microRNA mimics, microRNA inhibitors and related molecules that can regulate protein expression at the transcript level by exploiting endogenous cell mechanisms. Delivery of a TheraSilence-formulated anti-miR-145 molecule into rats with experimentally induced pulmonary arterial hypertension appeared to normalize vascular remodeling that occurs in the lung and help restore cardiac function that is compromised as a result of the disease. The findings from this study are consistent with the data observed in earlier preclinical studies. Development for RNA therapeutics has been significantly limited due to the delivery challenges associated with nucleic acid-based therapies, with development efforts in the space focused primarily on diseases of the liver. Our chemically-flexible approach offers the opportunity to significantly expand the development of RNA therapies to include major unmet medical needs affecting the lung, such as lung cancer, asthma and pulmonary hypertension.
