Porphyrin and phthalocyanine antiscrapie compounds.
The transmissible spongiform encephalopathies (TSEs) are fatal, neurodegenerative diseases for which no effective treatments are available. The likelihood that a bovine form of TSE has crossed species barriers and infected humans underscores the urgent need to identify anti-TSE drugs. Certain cyclic tetrapyrroles (porphyrins and phthalocyanines) have recently been shown to inhibit the in vitro formation of PrP-res, a protease-resistant protein critical for TSE pathogenesis. We now report that treatment of TSE-infected animals with three such compounds increased survival time from 50 to 300%. The significant inhibition of TSE disease by structurally dissimilar tetrapyrroles identifies these compounds as anti-TSE drugs.
Priola
S A
SA
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. spriola@nih.gov
Raines
A
A
Caughey
W S
WS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003905:Deuteroporphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018620:PrPSc Proteins / Q000187:drug effects* / Q000378:metabolism; D012608:Scrapie / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects; D013997:Time Factors
D003905:Deuteroporphyrins; D005290:Ferric Compounds; D007211:Indoles; D008665:Metalloporphyrins; D011166:Porphyrins; D018620:PrPSc Proteins; C404818:deuteroporphyrin IX 2,4-bis(ethylene glycol)iron III; C404817:meso-tetra(4-N-methypyridyl)porpine iron(III); C028418:tetrasulfophthalocyanine; C021096:tetra(4-N-methylpyridyl)porphine