IT CERTAINLY sounds like a wonder drug: a compound designed to speed up metabolism that will reduce levels of artery-clogging substances such as cholesterol, and lead to weight loss. A big weight loss. Monkeys that were given the drug for a week lost 7 per cent of their body mass.
Whether the approach will lead to a safe and effective drug remains to be seen. Several promising weight-loss drugs, such as leptin, have failed when tested in people.
The compound, KB-141, is a synthetic version of the thyroid hormones that increase the metabolic rate, making the body burn up more food and also reducing LDL cholesterol and lipoprotein (a), both risk factors for heart disease. However, natural thyroid hormones have serious side effects, in particular dangerous increases in heart rate.
Advertisement
But there are two different kinds of thyroid hormone detectors or 鈥渞eceptors鈥� in the body. Previous studies in humans and animals have revealed that only one type is responsible for setting the heart racing. So a team at biotech company Karo Bio of Huddinge, Sweden, looked for a molecule that acts specifically on the second receptor and came up with KB-141.
A group at Bristol-Myers Squibb in New Jersey compared the effects of KB-141 with the most common thyroid hormone. Like the natural hormone, KB-141 lowered cholesterol and increased oxygen consumption 鈥� a measure of metabolic rate 鈥� but it had little effect on heart rate (see Graphic). Obese monkeys given the drug lost up to 7 per cent of their body mass in seven days even though their diet hardly changed, and none suffered any adverse cardiac effects (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1633737100).
鈥淭he fact that they could separate out the metabolic properties is the real breakthrough,鈥� says David Carling, an obesity researcher at Imperial College London. But KB-141 may not be selective enough. Its effect on the beta receptor is only about 14 times as great as that on the alpha receptor: 100-fold selectivity would be better.
Whatever happens with KB-141 though, looking for drugs that turn up metabolism could be a more effective strategy than trying to develop ones that suppress the appetite, Carling says.