Predavanje »Open Flow Microperfusion«, metoda spremljanja farmakokinetike in farmakodinamike zdravil

 

Dr. Thomas Birngruber in Dr. Christoph Magnes, vodji raziskovalnih skupin na JOANNEUM RESEARCH, HEALTH, Gradec, Avstrija, bosta na predavanju z naslovom »Open Flow Microperfusion: the in-vivo analysis of monoclonal antibody treatment effects in atopic dermatitis« predstavila metodo odprte pretočne mikroperfuzije (Open Flow Microperfusion, OFM), ki omogoča spremljanje farmakokinetike in farmakodinamike zdravil v kožnem tkivu. Njihove klinične študije kažejo napovedno moč OFM pri dokazovanju klinične učinkovitosti zdravil v razvoju. Predstavila bosta tudi primere nadaljnje uporabe metode OFM, kot so testiranje biološke dostopnosti bioloških zdravil (mAb) ter OFM model ksenografta možganskega tumorja.

Predavanje bo potekalo v torek 10. septembra 2024 ob 15:00 v srednji predavalnici Medicinske fakultete UL na Korytkovi ulici 2 kot predavanje Slovenskega biokemijskega društva v sklopu gostovanja na Inštitutu za biokemijo in molekularno genetiko, Medicinske fakultete Univerze v Ljubljani. Predavanje bo potekalo v angleškem jeziku.

 

POVZETEK PREDAVANJA
Open Flow Microperfusion to investigate the in-vivo treatment effects of Dupilumab in atopic dermatitis leasonal and non-leasonal skin Dupilumab, a monoclonal antibody, has received approval for the management of atopic dermatitis (AD); nonetheless, its impact on molecular, cellular, and immunological levels necessitates further clarification. Within this investigation, blood and dermal interstitial fluid (ISF) were obtained from nonlesional (NL) and lesional (L) skin of eight patients diagnosed with moderate to severe AD, both prior to (visit 2-v2) and following a 16-week course of dupilumab treatment (visit 10-v10). The clinical efficacy of the treatment was evidenced by a notable reduction in AD severity scores at the treatment's conclusion. A comparison between v10 and v2 revealed a decrease in the proportions of CD4+ interleukin-producing cells in ISF L and NL, elevated unbound IL-4 levels in plasma (p < 0.0001), a decrease in IL-5 levels in ISF L (p = 0.042), and an increase in the levels of components related to anti-inflammatory pathways and reepithelization. Analysis at v2 indicated potential alterations in amino acid pathways and lipid signaling in ISF L compared to ISF NL. Conversely, at v10, ISF L displayed heightened levels of long- and very-long-chain fatty acids and lipids in comparison to v2. Additionally, administration of dupilumab led to a diminished expression of miR-155−5p and miR-378a-3p in ISF L. Ultimately, the outcomes of this study contribute novel insights by establishing connections between local immune responses, metabolic changes, and the pathogenesis of AD, along with the subsequent treatment outcomes.
Objavljeno v: https://pubs.acs.org/doi/10.1021/acs.jproteome.4c00153#