Unmet NeedAccording to WHO, over one billion people worldwide are living with elevated blood pressure which may lead to a range of adverse health conditions that cause ~1,100 deaths per day. Many current high blood pressure therapies focus on angiotensin receptor blocking drugs. Unfortunately, adverse events (e.g., renal dysfunction, hyperkalemia, and hypotension) limit the duration of their administration regimen. As such, there is a warranted need for new therapeutic strategies.
Technology OverviewRecently, Johns Hopkins researchers identified a ‘mitochondrial angiotensin system’ (MAS) with functional angiotensin II receptors. These mitochondrial based angiotensin II receptors offer novel targets for anti-inflammatory therapies that may improve the current standard of treatment. Building on this discovery, the investigators have developed a method for the targeted delivery of ‘mitochondrial angiotensin receptor blockers’ (MARBs) to the mitochondrial angiotensin system for the treatment of diseases caused by angiotensin-related mitochondrial dysfunction.
The invention describes a novel composition comprising the conjugation of a MARB therapeutic agent to a peptidyl ‘mitochondrial targeting signal’ (MTS), which selectively delivers therapeutic moieties to the desired component of the mitochondria (outer membrane, inter-membrane space, inner membrane or matrix). Furthermore, this type of conjugated modification can also be used to transport imaging agents (e.g., fluorophore) to selective zones of the mitochondrion for additional imaging studies.
By specifically targeting drugs to angiotensin II type 2 receptors in human mitochondria much lower doses will be needed thereby reducing the systemic side effects for treatments aimed at maintaining mitochondrial functions while reducing oxidative stress damage and potentially leading to improved muscle function, physical fitness and delay the signs of aging.
Stage of DevelopmentIn vitro data is available.
PublicationsLin R, et al. Bioconjug Chem. 2015 Jan 21;26(1):71-7
