Candidate drug for familial hypercholesterolaemia needs more work

doi:10.1136/bmj.334.7585.118

BMJ 2007;334:118 (20 January), doi:10.1136/bmj.334.7585.118

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Candidate drug for familial hypercholesterolaemia needs more work

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People with severe familial hypercholesterolaemiahave non-functioning receptors for low density lipoprotein (LDL)cholesterol. This defect leads to sky high serum concentrationsof total and LDL cholesterol, early cardiovascular disease,and death. Treatment options are limited because conventionaldrug treatments don't work, and LDL aphoresis—a kind ofcholesterol dialysis—is intensive, expensive, and notwidely available. Production of LDL cholesterol can be stoppedat its source, however, by inhibiting the hepatic protein thattransfers triglycerides on to apolipoprotein B to make verylow density lipoprotein, the precursor of LDL. Researchers recentlytested such an inhibitor (BMS-201038) in six adults with homozygousfamilial hypercholesterolaemia, and it had the desired effect.Their mean serum concentrations of LDL cholesterol fell from15.9 to 7.8 mmol/l, a significant fall of more than 50% (P<0.001).BMS-201038 had a similar effect on total cholesterol during16 weeks of treatment at an increasing dose

The researchers were pleased with the resultsbut say their new compound is unlikely to get much further untilthey sort out its adverse effects on the liver. Concentrationsof liver enzymes went up substantially in four of the six patients,and the same number developed a fatty liver. By the end of thestudy, two patients had a hepatic fat content of 30%.