Predicting age of onset and progression of disease in late-onset genetic neurodegenerative diseases: An ethics review and research agenda

Abstract

Currently, a prognostic biomarker-based model is being developed to predict the onset and disease progression of Huntington's Disease (HD) and Spinocerebellar Ataxia (SCA) types 1 and 3, both late-onset genetic neurodegenerative diseases lacking a disease-modifying treatment (DMT). The need for more accurate predictions of onset and disease progression arises in the context of clinical trials evaluating the effectiveness of potential DMTs and identifying the optimal time to initiate such a DMT. Moreover, such a prognostic model may provide mutation carriers with personal utility. The aim of this article is to anticipate the ethical issues raised by these new prognostic models and to formulate the ethical issues that need to be addressed to facilitate an ethically responsible development and implementation of such a model. Part one of this article describes the ethical issues raised by presymptomatic genetic testing for HD and evaluates whether and how these issues may also occur by predicting onset and disease progression. Part two presents the results of a critical interpretative review into the ethical issues raised by biomarker testing in other late-onset neurodegenerative diseases lacking a DMT. The review aims to identify new ethical issues related to biomarker testing for predicting the onset and disease progression of HD and SCA. Finally, based on parts one and two, part three proposes a research agenda for the near future regarding the most pressing ethical issues that need to be addressed to ensure an ethically responsible implementation of such a prognostic model in both research settings and clinical practice.