JHU Ref #: C17482
Value Proposition
· Effective & Targeted: Harnesses endogenous pain signaling via receptor tyrosine kinases to conditionally deliver effector proteins to the plasma membrane, enabling suppression of chronic pain under pathological conditions
· Broadly Applicable: Enables modular, tunable therapy tailored to the prevailing pathological condition, expanding potential applications to neurological conditions, immune disorders, cancer, and metabolic abnormalities
· Research Possibilities: Provides a means of visualizing receptor tyrosine kinase activity in a range of cell types
Unmet Need
· Chronic pain is defined as pain that persists most days or every day for three months or more. In the United States, approximately 51.6 million adults experience chronic pain, and among them, 17.1 million suffer from high-impact chronic pain that limits daily life and work activities (US Pain Foundation).
· Current therapies for chronic pain remain inadequate due to limited effectiveness, challenges with dosing or timing, and undesirable side effects. In the United States, approximately 22.1% of adults with chronic pain use opiates and opioids, which carry significant risks of dependence, addiction, and overdose (National Health Statistics Report).
· Thus, there exists a strong need to develop a safer and more effective therapeutic approach for suppressing chronic pain.
Technology Description
· Current therapies for chronic pain have limited effectiveness and are associated with adverse and potentially dangerous side effects. Researchers at Johns Hopkins have developed a technology that utilizes endogenous receptor tyrosine kinase signaling to trigger the conditional delivery of effector proteins to combat neurological conditions, immune disorders, cancer, and metabolic abnormalities. This is accomplished by a “protease” module that binds to an activated RTK and a “carrier” module that binds to the same activated RTK, containing a latent effector domain capable of localization to the plasma and endosomal membrane compartments to inhibit or activate target GTPases. Genetically based delivery of this system provides the opportunity to achieve selective production of the pain-inhibiting end product only in sensory neurons, thus enabling selective engagement of signaling pathways fundamental to pain that could otherwise never be safely targeted using conventional pharmacological approaches, given their ubiquitous expression in other cell types. This technology’s current embodiment leverages endogenous pain signaling via receptor tyrosine kinases to achieve the conditional delivery of effectors that suppress chronic pain.
Stage of Development
· In vitro experiments have been conducted, demonstrating successful RTK-dependent, protease-dependent, and effector protein translocation in transfected HEK293 cells. Functional validation includes inhibition of MAPK signaling (mediates chronic pain) via an acylated effector protein.
Data Availability
· Data available upon request.
Publication
WO2024102436A1: System for modulating receptor tyrosine kinase signaling and methods of use thereof
