The Cost of Safety: Balancing Biosafety and Histologic Integrity in Prion Research

Abstract

Commentary Prion diseases, or transmissible spongiform encephalopathies (TSEs), represent a group of incurable and invariably fatal neurodegenerative disorders driven by the pathological misfolding of the prion protein (PrP) [1-6]. These diseases are characterized by a progressive clinical course and, despite their significant impact on human [7-17] and animal [1,10,18-30] health, currently lack effective therapeutic interventions [31-34] and are limited in early-stage diagnostics [1,7,31-33]. Given the broad host range of prion diseases, together with the absence of effective treatments and limited antemortem diagnostic options, continued prion disease research remains essential. However, research and clinical investigations of prion diseases present substantial occupational biosafety risks [35,36] because infectious prion proteins are highly resistant to many conventional decontamination procedures. In fact, because prions are misfolded proteins rather than microorganisms, they exhibit exceptional resistance to conventional decontamination methods, exceeding that of most microbial pathogens [37,38]. As a result, specialized and rigorous prion inactivation protocols are required for minimizing potential exposure in laboratory and clinical settings [39,40]. Formic acid treatment has been demonstrated to reduce prion infectivity and is commonly incorporated into biosafety practices for the decontamination of prion-contaminated tissues [6,23,41] and materials, however, the morphologic effects of formic acid decontamination on tissues was not reported previously. Our recently published study, Shabaan et al. [6], evaluated the morphologic effects of formic acid treatment on central nervous system (CNS) brain tissue using brain hemispheres from transgenic mouse models with variable degrees and patterns of neurodegeneration, see Table 1. The potential influence of age on tissue morphology following treatment was also assessed. Formic acid-treated tissues were