Speaker 

Dr Heywood is a GOSH BRC Principal Research Fellow and group leader in Translational Mass Spectrometry. She is also an Honorary Clinical Biochemist at Great Ormond Street Hospital and Director and co-founder of the UCL spin out Guilford Street Laboratories.

Dr Heywood’s research group focuses on developing biomarkers in Lysosomal Storage Disorders such as Neuronal Ceroid Lipofuscinosis (Battens disease), Niemann Pick C disease and the Glycosphingolipidoses disorders (Fabry, Gaucher & Krabbe disease). 

With expertise in proteomics and lipidomics for biomarker discovery and understanding disease mechanisms Dr Heywood’s group develops novel targeted multiplex assay panels for clinical applications such as clinical trials and supporting development of novel therapies. Her group has particular focus on supporting active collaborations with clinical partners to develop and streamline translation of novel biomarkers.

More information here.

New methods of monitoring anti-drug antibodies in LSD

Anti-drug antibodies (ADAs)  are a serious complication that can limit effectiveness of treatment and in some cases cause adverse events. Enzyme replacement therapies (ERT) for Fabry disease have seen life expectancy of patients extend up to 15 years. However up to 40% of male patients develop anti-drug antibodies limiting their effectiveness. ELISA based assays to detect ADAs lack standardisation between pharma independent laboratories limiting access to this resource for many clinicians.

I will be presenting on an alternative and innovative approach to antibody analysis using a ‘bait and capture’ technique combined with direct targeted multiplex proteomic analysis using mass spectrometry. The Immuno Targeted Anti-Drug Antibody (Immuno-TADA) platform was initially created to measure antibodies to SARS-CoV2 and enables easy adaptation to different bait antigens due to internal standardization of the bait protein.  We have now developed Immuno-TADA for measurement of a ADAs to agalsidase alfa, agalsidase  beta and pegunigalsidase alfa. Immuno TADA can measure the entire bound immune complex in 15uL of patient serum. This includes IgG1-4, IgA1-2, IgE, IgM and complement (C3-C9). Ratioing bound immunoglobulin to bait protein ERT improves accuracy and provides a quantitative read out of ng/ng of ERT. 

Application to Fabry patient samples confirms previous ELISA studies of ADA positivity rates in females at 16-18% and 25% in males. IgG4 appears to be the main neutralising immunoglobulin in male patients correlating with plasma Lyso-Gb3 and enzymatic inhibition. We are now working to offer immuno-TADA as a service to the Fabry clinical community through the NHS by end of 2025. 

Beyond IgG I’ll present interesting findings indicating IgA plays an undefined role in ADA immunogenicity and complement binding could have implication to adverse infusion events. I’ll also give a sneak preview of the application of Immuno TADA to anti-AAV therapies.