An interactive discussion on novel and exciting experimental medicine approaches to understand and treat metabolic dysfunction–associated steatotic liver disease (MASLD) 

The Rise of M1UK: Understanding the New Threat of Group A Streptococcus

Two recent Lancet publications will be used to highlight some of the challenges, successes and lessons learned from conducting clinical trials on brain infections in the UK and globally. 

Welcome to the Consult Series, featuring conversations with leading experts from across medicine, research, and healthcare innovation.

In this series, Professor Paul Klenerman and guest speakers join us to discuss their work, insights, and experiences at the forefront of medical research and clinical practice. Through engaging discussion and expert commentary, the series explores the latest developments shaping healthcare today, as well as the challenges and opportunities facing the future of medicine.

The Consult Series provides a platform for thought-provoking conversations designed to inform, educate, and inspire clinicians, researchers, and the wider medical community.

These recent papers describe work in the field of stromal cell biology. Fibroblasts were long regarded as simple structural cells and often ignored by immunologists. In these studies of human disease Chris Buckley discusses how recent approaches based on transcriptomics have shone new light on these cells and their role in disease. Given their long lived nature and capacity to remain resident in tissues, they may play particular roles in chronic inflammation. New data allows subsets of such cells to be delineated and potentially in future targeted to provide new therapies in inflammatory disease. Importantly, Prof. Buckley talks here (and in a recent webinar hosted by the Association of Physicians) about how innovative approaches to inflammatory disease can allow targeting of multiple different diseases, based on a deep understanding of the underlying pathology.

Characterization of a pathogenic nonmigratory fibroblast population in systemic sclerosis skin.

Clark KE, Xu S, Attar M, Ong VH, Buckley CD, Denton CP.JCI Insight. 2025 Apr 15;10(10):e185618. doi: 10.1172/jci.insight.185618. eCollection 2025 May 22.PMID: 40232859 Free PMC article.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Nayar S, Turner JD, Asam S, Fennell E, Pugh M, Colafrancesco S, Berardicurti O, Smith CG, Flint J, Teodosio A, Iannizzotto V, Gardner DH, van Roon J, Korsunsky I, Howdle D; Roche Fibroblast Network Consortium; Frei AP, Lassen KG, Bowman SJ, Ng WF, Croft AP, Filer A, Fisher BA, Buckley CD, Barone F.Nat Commun. 2025 Jan 2;16(1):5. doi: 10.1038/s41467-024-54686-0.PMID: 39747819 Free PMC article.

Wnt signaling drives stromal inflammation in inflammatory arthritis.

Mueller AA, Zou AE, Marsh LJ, Kemble S, Nayar S, Watts GFM, Murphy CL, Taylor E, Major T, Gardner D, Buckley CD, Wei K, Raychaudhuri S, Korsunsky I, Filer A, Croft AP, Brenner MB.bioRxiv [Preprint]. 2025 Jan 8:2025.01.06.631510. doi: 10.1101/2025.01.06.631510.PMID: 39829745 Free PMC article. Preprint.

Mark Hull talks about the translational research development of the n-3 PUFA EPA as a cancer prevention agent through to phase 2 and 3 clinical trials, touching on design and delivery of trials of ‘nutraceuticals’ like high-dose n-3 PUFAs, and how such an intervention might impact on cancer. Despite proof of concept from a small, randomised trial of EPA in patients with familial adenomatous polyposis, the same dose and formulation of EPA did not reduce overall colorectal polyp risk in the seAFOod polyp prevention trial. Emphasising the importance of the trial tissue biobank, he discusses a secondary genetic analysis of the seAFOod trial, which has uncovered a putative biomarker of EPA response that is more prevalent in people of African and Asian ancestry than those of White European heritage. This highlights the importance of patient diversity in clinical trials. He finishes by discussing latest epidemiological data on dietary n-3 PUFA intake (mainly from fish) and colorectal cancer risk.

Professor Paul Klenerman

Sidney Truelove Professorship of Gastroenterology, Nuffield Department of Medicine; Fellow of Green Templeton College, University of Oxford

Professor Mark Hull 

PhD FRCP, Leeds Institute of Medical Research, University of Leeds

The opinions of our host and guests are their own; AoP does not endorse any individual viewpoints, given products or companies.

Immune thrombocytopenia (ITP) is a rare autoimmune disease, but also one where a great deal of progress has been made in development of new therapies. Prof Cooper performs clinical trials to understand the impact of new therapies, based upon and also gaining insights into the underlying pathogenesis. The clear readout of platelet count allows for a trial design which can funnel diverse new types of therapy into the translational pathway, and this sort of study has implications more broadly for how we address auto-immunity more generally. This work is a great example of how fundamental understanding of pathology can be turned into new therapies for patients by clinician scientists working at the interface.

The papers discussed look at the role of immune modulation in auto-immune thrombocytopenia, and trial approaches using inhibition of neonatal Fc receptors, as well as inhibition of the BTK molecule. More broadly we discuss the pathogenesis of this disease, how trials are performed and the landscape for future studies.

Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study.

Kuter DJ, Ghanima W, Cooper N, Liebman HA, Zhang L, Hu Y, Miyakawa Y, Homenda W, Galindo LEM, Basquiera AL, Tan CW, Saydam G, Hütter-Krönke ML, Chai-Adisaksopha C, Gómez-Almaguer D, Tran H, Shin HJ, Dantas da Cunha Junior A, Lazar Z, Izquierdo CP, Kirgner I, Lucchini E, Kuzmina G, Fillitz M, Audia S, Taparia M, Cordoba M, Diab R, Yao M, Gouia I, Lee M, Daak A.

Blood. 2025 Jun 12;145(24):2914-2926. doi: 10.1182/blood.2024027336.

PMID: 40090011

Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double-blind, placebo-controlled phase 3 studies and their open-label extension.

Cooper N, Bussel JB, Kaźmierczak M, Miyakawa Y, Cluck S, Lledó García R, Haier B, Lavrov A, Singh P, Snipes R, Kuter DJ.

Br J Haematol. 2025 Feb;206(2):675-688. doi: 10.1111/bjh.19858. Epub 2024 Nov 18.

PMID: 39552477 

The role of genetic sequencing in the diagnostic workup for chronic immune thrombocytopenia.

Joshi N, Lango-Allen H, Downes K, Simeoni I, Vladescu C, Paul D, Hart A, Ademokun C, Cooper N.

Blood Adv. 2025 Apr 8;9(7):1497-1507. doi: 10.1182/bloodadvances.2024014639.

PMID: 39808791 

Related studies

https://www.nejm.org/doi/full/10.1056/NEJMcp1810479

Professor Paul Klenerman
Sidney Truelove Professorship of Gastroenterology, Nuffield Department of Medicine; Fellow of Green Templeton College, University of Oxford

Professor Sir Munir Pirmohamed, MB ChB (Hons), PhD, FRCP, FRCP(E), FFPM, FRSB, FBPhS, FMedSci: Linking genes and drugs. 

 Click here to view the paper