Preventive pharmacological treatment in subjects at risk for fatal familial insomnia: science and public engagement. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Forloni, Gianluigi; Roiter, Ignazio; Artuso, Vladimiro; Marcon, Manuel; Colesso, Walter; Luban, Elviana; Lucca, Ugo; Tettamanti, Mauro; Pupillo, Elisabetta; Redaelli, Veronica; Mariuzzo, Francesco; Boscolo Buleghin, Giulia; Mariuzzo, Alice; Tagliavini, Fabrizio; Chiesa, Roberto; Ambrosini, Anna
• Is Part Of: Prion. Volume 16:Issue 1(2022)
• Page Start: 66
• Page End: 77
• Publication Date: 2022-12-31
• Subjects: clinical trial -- disease incidence -- genetic prion diseases -- patient engagement -- tetracyclines; Protein folding -- Periodicals; Prions -- Periodicals; Proteins -- Biotechnology -- Periodicals; 572.633
• DOI: 10.1080/19336896.2022.2083435
• Languages: English
• ISSNs: 1933-6896

Abstract

ABSTRACT: Engaging patients as partners in biomedical research has gradually gained consensus over the last two decades. They provide a different perspective on health priorities and help to improve design and outcomes of clinical studies. This paper describes the relationship established between scientists and members of a large family at genetic risk of very rare lethal disease, fatal familial insomnia (FFI). This interaction led to a clinical trial based on the repurposing of doxycycline – an antibiotic with a known safety profile and optimal blood–brain barrier passage – which in numerous preclinical and clinical studies had given evidence of its potential therapeutic effect in neurodegenerative disorders, including prion diseases like FFI. The design of this trial posed several challenges, which were addressed jointly by the scientists and the FFI family. Potential participants excluded the possibility of being informed of their own FFI genotype; thus, the trial design had to include both carriers of the FFI mutation (10 subjects), and non-carriers (15 subjects), who were given placebo. Periodic clinical controls were performed on both groups by blinded examiners. The lack of surrogate outcome measures of treatment efficacy has required to compare the incidence of the disease in the treated group with a historical dataset during 10 years of observation. The trial is expected to end in 2023. Regardless of the clinical outcome, it will provide worthwhile knowledge on the disease. It also offers an important example of public engagement and collaboration to improve the quality of clinical science.