A 23-years-old male entered a safety clinical trial for
cetirizine (a selective
histamine H(1)-receptor antagonist) in combination with the
antibiotic erythromycin. Within a few weeks of finishing the trial, the patient reported bilateral vision loss with optic nerve
atrophy. Genetic studies showed that he had a
mitochondrial DNA (
mtDNA) mutation at position 11778 (within the gene for subunit 4 of
NADH-
coenzyme Q oxidoreductase), commonly associated with
Leber's hereditary optic neuropathy. To test if
erythromycin could worsen the mitochondrial respiratory chain defect associated with the 11778
mtDNA mutation, we transferred the patient's
mtDNA to cultured
mtDNA-less
osteosarcoma cells.
Erythromycin inhibited proliferation of the patient's transmitochondrial cybrids in conditions that required mitochondrial respiration for growth. We confirmed that
erythromycin is a potent inhibitor of mitochondrial translation in these cells. Taken together, these results suggest that
erythromycin may have hastened a bioenergetics crisis in the optic nerve of this patient. This association underscores the importance of being cautious with the use of drugs that interfere with cellular respiration in individuals with an underlying
mitochondrial dysfunction.