Assessing theoretical risk and benefit suggested by genetic association studies of CCR5: experience in a drug development programme for maraviroc.
2007
The proliferation of published gene association studies of the CCR5A32 mutation is of relevance to drug development of a CCR5 antagonist for HIV, in highlighting potential safety concerns. We conducted an initial review of all non-HIV gene association studies of CCR5-A32, followed by detailed meta-analyses in the three disease areas most commonly reported. Our review indicated no consistent evidence of increased risk of susceptibility to hepatitis C virus infection or multiple sclerosis among individuals with CCR5-A32 mutation, and suggested treatment with a CCR5 inhibitor is unlikely to have related adverse effects. There was, however, evidence to suggest rheumatoid arthritis as a potential therapeutic target for a CCR5 antagonist. Clinical evidence would be required to confirm these findings.
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