BSE (more commonly known as mad cow disease) and CJD, which is a related disease in humans that can occur spontaneously, be inherited, or be acquired (in some cases probably from cows with BSE), are fatal neurodegenerative diseases. It is thought that these diseases are caused by accumulation in the brain of an abnormally folded version (PrPsc) of a natural protein (PrPc). There are currently no therapies for the treatment of these diseases, making this an area of active investigation.
In a study appearing in the December issue of the Journal of Clinical Investigation, Alexander Pfeifer and colleagues from the University of Bonn, Germany, show that in mice silencing of the gene encoding PrPc suppresses the accumulation of PrPsc. In vitro, silencing the gene encoding PrPc, using a technique known as RNA interference (RNAi), in already diseased neurons suppressed the accumulation of PrPsc. Similarly, in mice engineered to express the gene silencing therapeutic in a varying proportion of their neurons, the accumulation of PrPsc was markedly delayed, with the delay in accumulation of PrPsc being directly correlated with the proportion of neurons in the brain expressing the gene silencing therapeutic. This study therefore provides hope that RNAi might provide a new approach for the development of a therapeutic to treat individuals and animals with neurodegenerative disorders such as CJD and BSE. However, as Qingzhong Kong from Case Western Reserve University says in an accompanying commentary “Much more research is needed before RNAi can be harnessed to treat…” these neurodegenerative disorders.
TITLE: Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice
AUTHOR CONTACT:
Alexander Pfeifer,
University of Bonn, Bonn, Germany.
Phone: +49-228-735410; Fax: +49-228-735404; E-mail: alexander.pfeifer@uni-bonn.de .
Hans Kretzschmar
University of Munich, Munich, Germany.
Phone: +49-89-2180-78001; Fax: +49-89-2180-78037; Email: hans.kretzschmar@med.uni-muenchen.de .
View the PDF of this article at: https://www.the-jci.org/article.php"id=29236
ACCOMPANYING COMMENTARY
TITLE: RNAi: a novel strategy for the treatment of prion diseases
AUTHOR CONTACT:
Qingzhong Kong
Case Western Reserve University, Cleveland, Ohio, USA.
Phone: (216) 368-1756; Fax: (216) 368-2546; E-mail: qxk2@case.edu .
View the PDF of this article at: https://www.the-jci.org/article.php"id=30663
Journal of Clinical Investigation