Administration of FK506 from Late Stage of Disease Prolongs Survival of Human Prion-Inoculated Mice.
Neurotherapeutics
; 17(4): 1850-1860, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32483654
ABSTRACT
Human prion diseases are etiologically categorized into three forms sporadic, genetic, and infectious. Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common type of human prion disease that manifests as subacute progressive dementia. No effective therapy for sCJD is currently available. Potential therapeutic compounds are frequently tested in rodents infected with mouse-adapted prions that differ from human prions. However, therapeutic effect varies depending on the prion strain, which is one of the reasons why candidate compounds have shown little effect in sCJD patients. We previously reported that intraperitoneal administration of FK506 was able to prolong the survival of mice infected with a mouse-adapted prion by suppressing the accumulation of abnormal prion protein (PrP) and inhibiting the activation of microglia. In this study, we tested oral administration of FK506 in knock-in mice expressing chimeric human prion protein (KiChM) that were infected with sCJD to determine if this compound is also effective against a clinically relevant human prion, i.e., one that has not been adapted to mice. Treatment with FK506, started either just before or just after disease onset, suppressed typical sCJD pathology (gliosis) and slightly but significantly prolonged the survival of sCJD-inoculated mice. It would be worthwhile to conduct a clinical trial using FK506, which has been safety-approved and is widely used as a mild immunosuppressant.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Síndrome de Creutzfeldt-Jakob
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Tacrolimus
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Progresión de la Enfermedad
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Proteínas Priónicas
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Inmunosupresores
Límite:
Aged
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Animals
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Female
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Humans
Idioma:
En
Revista:
Neurotherapeutics
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón