A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria.

Abstract

Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid 1,2-dioxygenase has recently been confirmed at the molecular level, no effective treatment regimen has yet been developed for this disorder. In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary output of homogentisic acid in a murine model of alkaptonuria that had been created with ethylnitrosourea. These findings suggest that NTBC may be the first potent pharmacotherapeutic agent for alkaptonuria.

• Authors: Y Suzuki, K Oda, Y Yoshikawa, Y Maeda, T Suzuki
• Journal: Journal of human genetics (J Hum Genet) Vol. 44 Issue 2 Pg. 79-84 ( 1999) ISSN: 1434-5161 [Print] England
• PMID: 10083729 (Publication Type: Journal Article)

Chemical References

• Cyclohexanones
• Enzyme Inhibitors
• Nitrobenzoates
• 4-Hydroxyphenylpyruvate Dioxygenase
• nitisinone
• Homogentisic Acid

Topics

• 4-Hydroxyphenylpyruvate Dioxygenase (antagonists & inhibitors)
• Alkaptonuria (blood, drug therapy, pathology)
• Animals
• Cyclohexanones (pharmacokinetics, therapeutic use)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacokinetics, therapeutic use)
• Homogentisic Acid (urine)
• Mice
• Mice, Mutant Strains
• Nitrobenzoates (pharmacokinetics, therapeutic use)