Background: Accidental transmission of Creutzfeldt-Jakob disease (CJD) has been reported after neurosurgical interventions, use of intracerebral electrodes, corneal transplants, and after the administration of human-derived hormones. Acquired CJD has also been documented after dural grafting with tissues of human cadaver origin. At present, quinacrine and chlorpromazine are being investigated for the treatment of sporadic CJD, with the hope of offering an effective treatment of an otherwise fatal disease. Our objective was to report a case of iatrogenic CJD occurring 18 years after the implant of a dural graft of human origin and to inform on the results of the treatment with quinacrine and chlorpromazine.
Case Description: In 1984, a 46-year-old woman was given a Lyodura graft for decompression of Chiari I malformation and syringomyelia. The patient was diagnosed with CJD in 2002. In view of the scarce options for treatment of CJD and after reviewing the current literature, the patient was treated with quinacrine and chlorpromazine. She showed no clinical improvement and died 6 months after hospital admission. The iatrogenic origin of the disease in this patient is supported by the clinical features, laboratory data, and findings from the brain necropsy.
Conclusions: Patients who have received a dural graft of cadaveric origin may be at risk for developing CJD after very prolonged incubation periods. Treatment with quinacrine and chlorpromazine for acquired CJD was ineffective in our patient. A clinical trial on the use of antiprion agents is warranted.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.surneu.2005.03.035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH.
J Med Chem
April 2021
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Quinacrine (QC) and chloroquine (CQ) have antimicrobial and antiviral activities as well as antimalarial activity, although the mechanisms remain unknown. QC increased the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localized in the yeast membranes and induced glucose starvation by noncompetitively inhibiting glucose uptake as antipsychotic chlorpromazine (CPZ) did.
View Article and Find Full Text PDFIdentification of compounds inhibiting prion replication and toxicity by removing PrP from the cell surface.
J Neurochem
January 2020
Dulbecco Telethon Laboratory of Prions and Amyloids, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Article Synopsis
- Most treatments for prion diseases have tried to attack the infective form of a protein called PrP, but they haven't worked well.
- Researchers found that a drug called chlorpromazine can help stop prion replication by moving PrP away from where it normally sits on the cell surface, but it's not safe for long-term use.
- They have now discovered four new compounds that can reduce PrP on the cell surface and one that can also stop prions from spreading, suggesting that getting rid of PrP from cells might be a good way to treat prion diseases.
Synthesis of conjugates of 6-aminophenanthridine and guanabenz, two structurally unrelated prion inhibitors, for the determination of their cellular targets by affinity chromatography.
Bioconjug Chem
February 2010
Laboratoire de Chimie Organique 2, INSERM U648, Universite Paris-Descartes, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
The synthesis of affinity matrices for 6-aminophenanthridine (6AP) and 2,6-dichlorobenzylidenaminoguanidine (Guanabenz, GA), two unrelated prion inhibitors, is described. In both cases, the same simple spacer, epsilon-aminocaproylaminopentanol, was introduced by a Mitsunobu reaction and the choice of the anchoring position of the linker was determined by the study of the residual antiprion activity of the corresponding 6AP or GA conjugates. Very recently, these two affinity matrices were used for chromatography assays leading to the identification of ribosome (via the rRNA) as a common target of these two antiprion drugs.
View Article and Find Full Text PDFInhibition of RNA recruitment and replication of an RNA virus by acridine derivatives with known anti-prion activities.
PLoS One
October 2009
Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
Background: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV), a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ) and quinacrine (QC), which are active against prion-based diseases.
Methodology/principal Findings: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts.
Multiple ligand-binding properties of the lipocalin member chicken alpha1-acid glycoprotein studied by circular dichroism and electronic absorption spectroscopy: the essential role of the conserved tryptophan residue.
Biochim Biophys Acta
August 2006
Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, Budapest, P.O. Box 17, H-1525, Hungary.
Multiple ligand-binding properties of the 30-kDa chicken alpha(1)-acid glycoprotein (cAGP), a member of the lipocalin protein family, were investigated for the first time by using circular dichroism (CD) and UV/Vis absorption spectroscopy methods. By measuring induced CD (ICD) spectra, high-affinity binding (K(a) approximately 10(5)-10(6) M(-1)) of several drugs, dyes and natural compounds to cAGP was demonstrated including antimalarial agents (quinacrine, primaquine), phenotiazines (chlorpromazine, methylene blue), propranolol, non-steroidal antiinflammatory drugs (ketoprofen, diclofenac), tamoxifen, diazepam, tacrine, dicoumarol, cationic dyes (auramine O, thioflavine T, ethidium bromide), benzo[a]pyrene, L-thyroxine, bile pigments (bilirubin, biliverdin), alkaloids (piperine, aristolochic acid), saturated and unsaturated fatty acids. Analysis of the extrinsic CD spectra with the study of the covalently modified protein and CD displacement experiments revealed that a single Trp26 residue of cAGP conserved in the whole lipocalin family is part of the binding site, and it is essentially involved in the ligand-binding process via pi-pi stacking interaction resulting in the appearance of strong induced CD bands due to the non-degenerate intermolecular exciton coupling between the pi-pi* transitions of the stacked indole ring-ligand chromophore.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!