✨Exciting to see clinical efficacy of peripheral #CB1R antagonism with #monlunabant. It will expand armamentarium for #obesity with an oral 💊therapy and a different mechanism than incretins ( #GLP1 #GIP)💉

⚡️Similar efficacies in all tested oral doses encourage testing lower doses to optimize safety.

🧵6️⃣ ⚡️Therapeutic modality to improve antifibrotic efficacy⚡️

📌 #Zevaquenabant treatment effectively reduces #fibrosis in human precision-cut lung slices (#hPCLS).

📌 Pulmonary delivery of zevaquenabant may offer a more targeted and safer #therapeutic modality for #fibrotic #lung #diseases

🧵5️⃣ ⚡️Therapeutic modality to improve antifibrotic efficacy⚡️

📌Systems #pharmacology reveals that #zevaquenabant and #nintedanib treatments reverse distinct and shared #pulmonaryfibrosis related pathways, provides opportunity for future clinical trials to improve clinical efficacy.

🧵4️⃣ ⚡️Therapeutic modality to improve antifibrotic efficacy⚡️

📌 #Zevaquenabant attenuates multiple #fibrosis-related pathways in lungs

📌 Pulmonary delivery of zevaquenabant attenuated #fibrogenic #macrophages expressing Spp1, Trem2, Tgfb1, Mertk, Fabp5, Cd9, Cd63, Gpnmb, Fabp4

🧵3️⃣ ⚡️Therapeutic modality to improve safety ⚡️

📌🫁Pulmonary delivery of #zevaquenabant (#MRI1867) by lowering the systemic dose 20-fold retains superior therapeutic efficacy in mitigating PF by eliminating systemic exposure in animal model of #PulmonaryFibrosis

🧵2️⃣ ⚡️Therapeutic target identification⚡️

📌 CB1R regulates #CD206-expressing macrophages and releases of #profibrotic mediators (IL-6, IL-4, LIF, GM-CSF, CXCL10, CCL7, CCL11, IGF-1).

📌 Inhibition of #CB1R in #AlveolarMacrophages attenuates #fibrogenic activation of Macrophages.

🧵1️⃣ ⚡️Therapeutic target identification ⚡️

📌 CB1R in #AlveolarMacrophages (AMs) is responsible to release #anandamide into #alveoli and to promote #fibrosis.

📌 CB1R in AMs plays a dominant role in pulmonary fibrosis by inducing fibrogenic macrophages.

📣Our work @jci-insight.bsky.social highlights the key role of #cannabinoid receptor 1 in #AlveolarMacrophages in promoting #PulmonaryFibrosis. We propose that pulmonary delivery of #zevaquanabant as an effective and safer therapeutic approach. Details in🧵👇https://insight.jci.org/articles/view/187967

‼️A post-doc position available in my lab at the NIH ‼️

⚡️Fibrosis Biology
⚡️Biomarker Discovery
⚡️Pharmacology
⚡️Therapeutic discovery
⚡️Translational research

See the position details👇

www.training.nih.gov/jobs/pdf-090...

#postdoc #medsky #Fibrosis

Please RT⚠️

Our research shows endocannabinoid anandamide in blood has biomarker functions in Hermansky-Pudlak syndrome. It not only captures early stage fibrosis progression in lung but also informs on therapeutic efficacy for CB1R antagonism.This may help to design effective anti-fibrotic therapy for #HPSPF