Lets talk about ataxia-telangiectasia: Meeting report of the AT clinical research conference June 2025

Almost fifty years after the identification of ataxia telangiectasia (A-T) as a radiosensitive disorder and thirty years following the identification of ataxia telangiectasia mutated (ATM) as the defective gene, clinicians and scientists gathered at Loughborough University, UK from June 25th -27th 2025 for an Ataxia Telangiectasia Clinical Research Conference. The mix of expertise of clinicians and scientists with basic and translational expertise ensured that a focus was on how to exploit our knowledge of ATM's function to clinical benefit. Considerable emphasis was placed on the role of ATM in the DNA damage response and the consequences in this multisystem disease, including the neurodegenerative phenotype. The increasingly recognized role of ATM in oxidative stress was also considered and how it was pertinent to mitochondrial dysfunction, metabolic abnormalities and energy metabolism in A-T. The implications of these roles of ATM in protecting the genome/cell and the development of new technology, such as organoids, were widely discussed in the clinical setting of patients with A-T. An important contribution to the meeting was the description of pathways /mechanisms that have led to the development of therapeutic approaches for A-T including the use of specific antisense oligonucleotides to restore ATM function in patients; delivery of full-length ATM cDNA to A-T cells; eDSP (formerly EryDex) that encapsulates dexamethasone sodium phosphate in a patient's own red blood cells and the use of small molecules (triheptanoin, nicotinamide riboside and N-acetyl leucine) to correct mitochondrial and metabolic function.