University of Pittsburgh researchers have developed a novel delivery formulation for small molecules to manipulate the adenosine triphosphate (ATP)/Adenosine (Ado) signaling axis. Using microparticle-based controlled release systems, an antagonist for an ATP receptor and/or agonists for Ado receptors can be delivered over a period of days to weeks, leading to reduced inflammation. Controlled release of these small molecules could reduce the need for repetitive administration of medication, reduce inflammation, and enhance patient quality of life.
Description
The ATP/Ado signaling axis is implicated in a wide variety of inflammatory diseases. ATP released from dying or activated immune cells can lead to increased inflammation through secretion of inflammatory cytokines (e.g., IL-1) and differentiation of effector immune cells (e.g., Th1, Th17). Extracellular ATP (eATP) can be converted to Ado leading to secretion of anti-inflammatory cytokines (e.g., IL-10) and inhibition of effector immune cell differentiation. Controlled release of antagonists and/or agonists in pico- or nano- gram quantities could inhibit ATP signaling and promote Ado signaling, reducing inflammation linked to numerous conditions.
Applications
- Inflammatory conditions
- Contact dermatitis
- Transplant rejection
Advantages
Current immunosuppressant therapies for inflammatory conditions often require daily administration of high concentrations of pharmaceutical agents to suppress inflammation. Additionally, due to their systemic administration and non-specific mechanism of actions, many existing therapies can lead to overimmunosuppression, increasing the risk of infections and other non-immune related side effects.
This novel approach involves a controlled release system that can encapsulate and release Ado receptor agonists and/or ATP receptor antagonists over time, reducing the need for high dosages of medication to be administered daily. This approach could potentially overcome the adverse effects associated with daily administration.
Invention Readiness
In vitro studies have demonstrated that the ATP antagonist, JNJ-55308942 (JNJ) can suppress inflammatory cytokine secretion (IL-1) and increase the percentage of FoxP3 expressing CD4+ T cells. In an animal model, daily injections of JNJ decreased inflammation-related swelling and reduced dermal and epidermal thickening. Microparticle-based controlled release systems have been developed to deliver JNJ as well as known AR agonists Regadenoson, or IB-MECA with sustained release observed of at least two weeks.
IP Status
Patent Pending
