Sporadic Creutzfeldt-Jakob disease: Real-Time Quaking Induced Conversion (RT-QuIC) assay represents a major diagnostic advance

Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and fatal neurodegenerative disorder with an incidence of 1.5 to 2 cases per million population/year. The disease is caused by a proteinaceous infectious agent, named prion (or PrPSc), which arises from the conformational conversion of the cellular prion protein (PrPC). Once formed, PrPSc interacts with the normally folded PrPC coercing it to undergo similar structural rearrangement. The disease is highly heterogeneous from a clinical and neuropathological point of view. The origin of this variability lies in the aberrant structures acquired by PrPSc. At least six different sCJD phenotypes have been described and each of them is thought to be caused by a peculiar PrPSc strain. Definitive sCJD diagnosis requires brain analysis with the aim of identifying intracerebral accumulation of PrPSc which currently represents the only reliable biomarker of the disease. Clinical diagnosis of sCJD is very challenging and is based on the combination of several clinical, instrumental and laboratory tests representing surrogate disease biomarkers. Thanks to the advent of the ultrasensitive Real-Time Quaking-Induced Conversion (RT-QuIC) assay, PrPSc was found in several peripheral tissues of sCJD patients, sometimes even before the clinical onset of the disease. This discovery represents an important step forward for the clinical diagnosis of sCJD. In this manuscript, we present an overview of the current applications and future perspectives of RT-QuIC in the field of sCJD diagnosis.

Doença de Creutzfeldt-Jakob: um relato de caso da forma esporádica

“…No presente momento, várias intervenções terapêuticas potenciais já foram testadas, mas nenhum tratamento se provou eficaz. 25 Em contrapartida, os recentes avanços em relação à compreensão da patogênese da DCJ, aumentaram a expectativa pelo surgimento de intervenções terapêuticas eficazes. 26 Neste contexto, a abordagem com o uso do medicamento antipsicótico Clorpromazina vem sendo utilizada visando a eliminação de príons, com bons resultados em camundongos até o momento, mas ainda sem expectativa de ser testada em seres humanos.…”

Application of real-time quaking-induced conversion in Creutzfeldt–Jakob disease surveillance

“…It was first established in 2011 [ 14 ] in cerebrospinal fluid and based on earlier methods using cyclic amplification [ 15 ]. The method is also able to detected PrP Sc seeding activity in other tissues such as olfactory mucosa, skin, and retina [ 16 ]. The diagnostic accuracy of CSF RT-QuIC was evaluated in multiple studies that reported sensitivities between 77 and 97% and specificities of > 99% [ 12 ].…”