evodenoson (ATL313) / AbbVie - LARVOL DELTA

"El nostre nou estudi a @naturemedicine segueix les passes del nostre estudi #ConsensCOVID sobre com acabar amb la #COVID19 com una amenaça per a la #salutpública, que compta amb 386 coautors de 112 països. 🔗 https://t.co/u92yahQ5GG" (@JVLazarus)

Infectious Disease • Novel Coronavirus Disease

Adenosine Receptors Differentially Mediate Enteric Glial Cell Death And Proinflammatory Response Induced By Clostridioides Difficile Toxins A And B (ASM Microbe 2022) - "A2A agonist (ATL313), but not A2A antagonist (SCH58261), decreased (p<0.001) apoptosis as detected by the formation of Phosphatidylserine-annexin binding and caspase 3/7 activity induced by TcdA and TcdB in EGCs...A3 agonist (Cl-IBMECA), but not A3 blocker (MRS1220), reduced apoptosis in EGCs challenged with TcdA and TcdB...In vivo, infected A2B KO mice, but not A2A, exhibited a lower percentage of S100B+TUNEL+cells compared to infected WT mice (p<0.0001). Our findings indicate that EGCs elicit a protective anti-inflammatory, via activation of A2A, A2B and A3, and anti-apoptotic, via upregulation of A2A and A3 and downregulation of A2B, responses against C. difficile toxins."

Gastrointestinal Disorder • Infectious Disease • Inflammation • ANXA5 • CASP3 • CASP7 • IL6

Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohn's Disease? (PubMed, Dis Colon Rectum) - "Smoking cessation after primary ileocolic resection for Crohn's disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86."

Journal

A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats. (PubMed, Brain Behav Immun) - "AR agonist actions at the nerve injury site suppress neuroinflammation, as reflected by decreased release of interleukin-1β and nitric oxide, as well as decreased sciatic expression of markers of monocytes/macrophages and inducible nitric oxide synthase. Taken together, the data are supportive that AR agonists, acting at the level of peripheral nerve injury, may be of therapeutic value in treating chronic pain of neuroinflammatory origin."

Journal • Preclinical

Sustained Reversal of Central Neuropathic Pain Induced by a Single Intrathecal Injection of Adenosine A2A Receptor Agonists. (PubMed, Brain Behav Immun) - "A single intrathecal injection of the A2AR agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine HCl (CGS21680) reversed SCI-induced allodynia for at least 6 weeks. A second A2AR agonist, 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313), was also able to significantly prevent and reverse SCI-induced allodynia for several weeks after a single intrathecal injection, providing converging lines of evidence of A2AR involvement. The enduring pain reversal after a single intrathecal injection of A2AR agonists suggests that A2AR agonists could be exciting new candidates for treating SCI-induced central neuropathic pain."

Journal