Ataxia-telangiectasia clinical trial landscape and the obstacles to overcome.

introductionAtaxia telangiectasia (A-T) is a life-limiting autosomal recessive disease characterized by cerebellar degeneration, ocular telangiectasias, and sinopulmonary disease. Since there is no cure for A-T, the standard of care is primarily supportive. AREAS COVERED: We review clinical trials available in PubMed from 1990 to 2023 focused on lessening A-T disease burden. These approaches include genetic interventions, such as antisense oligonucleotides, designed to ameliorate disease progression in patients with select mutations. These approaches also include pharmacologic treatments that target oxidative stress, inflammation, and mitochondrial exhaustion, to attenuate neurological progression in A-T. Finally, we discuss the use of biological immunotherapies for the treatment of malignancies and granulomatous disease, along with other supportive therapies being used for the treatment of pulmonary disease and metabolic syndrome. EXPERT OPINION: Barriers to successful genetic and pharmacologic interventions in A-T include the need for personalized treatment approaches based on patient-specific ATM mutations and phenotypes, lack of an animal model for the neurologic phenotype, and extreme rarity of disease making large-scale randomized trials difficult to perform. Ongoing efforts are needed to diagnose patients earlier, discover more effective therapies, and include more individuals in clinical trials, with the goal to lessen disease burden and to find a cure for patients with A-T.