10 Aug Injections of Adenosine into Mouse Joints Reversed Osteoarthritis
MedicalResearch.com Interview with:
Bruce N. Cronstein, MD
Paul R. Esserman Professor of Medicine
NYU School of Medicine
Director, NYU-H+H Clinical and Translational Science Institute
Director, Division of Translational Medicine
NYU Langone Health
New York, NY 10016
MedicalResearch.com: What is the background for this study?
Response: Osteoarthritis is the most common type of arthritis affecting about 10% of the adult population and 25% of the population over 60. We had previously found that adenosine, a molecule generated by nearly all cell types, is critical for maintaining cartilage health by activating specific adenosine receptors on the surface of cells (A2A receptors). Moreover, giving adenosine into the joint could prevent deterioration of cartilage (progression of osteoarthritis) in a rat model of osteoarthritis. Because people do not usually go for treatment of osteoarthritis until they have developed symptoms we asked whether administration of adenosine or adenosine that had been modified to be a more potent and specific stimulus for A2A receptors, carried in fat bubbles called liposomes, could reverse osteoarthritis after it had already started.
MedicalResearch.com: Would you briefly explain what adenosine is?
Response: Adenosine is a nucleic acid that, in modified form, is incorporated into DNA and RNA. Adenosine is also highly abundant in cells as an energy storage molecule (ATP). ATP is exported from cells where it can be broken down to adenosine which can bind to a family of receptors among which is the A2A receptor. Adenosine has a very short life outside of cells because it is metabolized to an inactive form by plasma enzymes and taken up by cells to be reconverted to ATP inside of the cell. The rapid disappearance of adenosine creates some difficulty in administering adenosine as a drug but also limits potential toxicity since adenosine receptors are nearly ubiquitous on cells throughout the body and mediate effects on blood pressure, heart rate and wakefulness (adenosine is one of the substances that helps put you to sleep at night) among many others.
MedicalResearch.com: What are the main findings?
Response: The central finding of this study is that if you treat mice with injections of adenosine or an A2A receptor agonist in liposomes that much of the damage already present in the arthritic joints is reversed in a mouse model of osteoarthritis. We also reported results of studies that suggest mechanisms by which A2A receptor stimulation helps to reduce joint injury.
MedicalResearch.com: What should readers take away from your report?
Response: The take-home message from these studies is that injection of adenosine or more specific adenosine receptor stimuli may be useful in reversing the changes associated with osteoarthritis.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The next research that my laboratory is doing is to better understand the mechanisms by which adenosine, acting at its receptors, prevents progression of osteoarthritis and contributes to its resolution. We obviously would like to determine whether adenosine can be used by people and their dogs and cats (osteoarthritis affects pets as well as humans).
MedicalResearch.com: Is there anything else you would like to add?
Response: Dr. Corciulo and I have formed a company, Regenosine, which will bring adenosine injections to people with osteoarthritis to ameliorate and reverse osteoarthritis and we continue to own shares in this company. NYU School of Medicine also owns shares in Regenosine.
Corciulo, C., Castro, C.M., Coughlin, T. et al. Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis. Sci Rep 10, 13477 (2020). https://doi.org/10.1038/s41598-020-68302-w
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