{"id":1797,"date":"2025-11-21T14:32:24","date_gmt":"2025-11-21T14:32:24","guid":{"rendered":"https:\/\/sites.manchester.ac.uk\/alport-hub\/?p=1797"},"modified":"2026-03-25T09:49:44","modified_gmt":"2026-03-25T09:49:44","slug":"newsletter-edition-1","status":"publish","type":"post","link":"https:\/\/sites.manchester.ac.uk\/alport-hub\/2025\/11\/21\/newsletter-edition-1\/","title":{"rendered":"Newsletter Edition #1"},"content":{"rendered":"

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It\u2019s our third year, and there are more things to report on than we could have imagined. We\u2019ll only be able to point to some of these in each edition.<\/p>\n

Hub research has two key elements: the Physical Hub means the Lennon Lab group in Manchester and collaborators elsewhere; and the Virtual Hub includes research into human disease via genetics, epidemiology, and clinical studies. The 1200+ patients in the RaDaR renal rare disease registry are key to this research.<\/p>\n

Physical Hub<\/h2>\n

Systematic assessment of variants<\/h3>\n

Complementary methods to to evaluate the functionality of genetic variants in collagen IV genes. In vitro assays and in vivo testing systems. Some assays also permit early testing of some therapeutic approaches.<\/p>\n

Specialist analysis of treatment effects<\/h3>\n

In animals and patients – a platform for complex assessment of protein expression and distribution in biopsies and samples from animal research or clinical trials.<\/p>\n

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Immunofluorescence image of a healthy human glomerulus using pan-collagen IV antibody (green; ab6586) and collagen IV alpha 3 antibody (red; Chondrex 7076 (H31), imaged on a Zeiss Axio Imager.D2 microscope (Bioimaging Core Facility, FBMH, University of Manchester).<\/em><\/p><\/div>\n

Molecular pathways influenced by therapy<\/h3>\n

Elucidating molecular pathways influenced by treatment. We know that ACE inhibitors work – do we understand how and why (by examining protein expression and proteomics). A parallel study is looking at the second approved preventive therapy for patients, SGLT2 inhibitors.<\/p>\n

Analysis of matrix turnover<\/h3>\n

Validating data from proteomic studies in Alport mice. Links to our biomarker studies (to be mentioned next time).<\/p>\n

AI-based system to analyse basement membranes<\/h3>\n

Focused on the changes in morphology of the glomerular basement membrane (GBM) of the Alport kidney.<\/p>\n

Virtual Hub<\/h2>\n

RaDaR cohort development<\/h3>\n

Maximising enrolment of patients, and ensuring that they have a minimum dataset, is critical to both understanding more about risk to individuals, and identifying those who may be eligible for new treatments. We are speaking individually to staff in RaDaR recruitment centres.<\/p>\n

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Map of the UK visualising Hub engagement with RaDaR sites<\/em><\/p><\/div>\n

Audiograms<\/h3>\n

We have begun to test with audiologists how to add data to RaDaR. The hearing problems of Alport patients have been largely neglected by previous research.<\/p>\n

Genetic tests<\/h3>\n

From the two major sequencing centres in the UK have been added to RaDaR records, enabling identification of patients with mutations that may be amenable to specific treatments, possibly including gene therapy.<\/p>\n

Genomics of Alport Syndrome<\/h3>\n

We are planning for whole genome sequencing of the RaDaR cohort, including a series of regional events.<\/p>\n

Key Publications<\/h2>\n

We\u2019ve picked just 5 to highlight here, for a comprehensive list please visit the Hub\u00a0Website<\/a>.<\/p>\n

Preston R et al 2025. The glomerular circadian clock temporally regulates basement membrane dynamics and the podocyte glucocorticoid response. Kidney Int 107:99-115.<\/p>\n

Gale DP et al 2024. HERA Clinical Trial Group. A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome. Clin J Am Soc Nephrol 19:995-1004<\/p>\n

Tian P et al 2024. Collagen IV assembly is influenced by fluid flow in kidney cell-derived matrices. Cells Dev 179:203923.<\/p>\n

Ng NSL et al 2024. Detection of Alport gene variants in children and young people with persistent haematuria. Pediatr Nephrol 40:719-729.<\/p>\n

Wong K et al 2024. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. Lancet 403:1279-1289 (Alport in supplementary data)<\/p>\n

‘Deep Dive’<\/h2>\n

International Workshop on Alport Syndrome – Beijing<\/a> 2025<\/h3>\n

This amazing meeting in September brought together leading researchers, clinicians, patients, and pharma from around the world for 3 days. 150 attended a patients-only day and some stayed throughout. The collaborative ethos of these workshops is remarkable amongst rare kidney diseases. The UK team contributed a dozen talks and was involved in almost all parts.<\/p>\n

? Meeting insights<\/h3>\n