Alexandria, DC from University of Cambridge, is focused on discovering biomarkers to be used to measure treatment-response in patients with Ataxia Telangiectasia (AT). AT is a multisystem disease including neurodegeneration. Currently there are only symptomatic treatments in part due to the lack of clinically meaningful biomarkers.
There are two forms of AT, classic and variant, with the latter having later onset and less severity. They can be differentiated based on the amount of ATM kinase activity with no activity in classic and little activity in variant AT. This is due to a broad range of mutations that lead to a diagnosis of AT.
Some mutations leading to variant AT have been identified as targetable by antisense oligonucleotide (ASO) therapy. ASO therapy has been developed in a few centres to target single ATM mutations, but there is an urgent need to identify measurable biomarkers to assess treatment on a single patient level. Alexandria’s goal is to create novel biomarkers to move forward testing ASOs for efficacy and toxicity. She is using cellular models such as skin fibroblasts, stem cell-derived neuronal cells and serum from patients.
To identify potential biomarkers, Alexandria studies the levels of multiple proteins with the technique called proteomics in patient serum and cell samples. Proteomics is the quantification of different proteins in a sample using mass spectrometry. The proteins that are calculated to be significantly reduced or increased in patient samples will be validated using other more selective quantification techniques measuring the levels of single proteins. After assessing the suitability of these models to model the cellular defect in AT, we hope to identify better biomarkers modelling the neurological symptoms in AT. These will facilitate clinical trials and the development of novel therapies.