AIDS-related lipodystrophy - TH-9507
AIDS-related lipodystrophy is a metabolic complication, characterised by fat accumulation in the abdomen, loss of subcutaneous fat and increased blood cholesterol and sugar. These are all risk factors for cardiovascular disease and Type II diabetes.
AIDS-related lipodystrophy is a metabolic complication, characterised by fat accumulation in the abdomen, loss of subcutaneous fat and increased blood cholesterol and sugar. These are all risk factors for cardiovascular disease and Type II diabetes.
Patients with the condition have reduced levels of growth hormone, but injections of the hormone cannot replicate the pulsatile pattern of endogenous secretion, and side-effects often result. Growth hormone is released by the anterior pituitary gland in response to growth hormone-releasing factor (GHRF), which is secreted by the hypothalamus. If this hormone were administered instead, it may be able to mimic the effect of natural growth hormone secretion and thus eliminate side-effects.
However, it has only a short half-life on injection, so longer-lasting GHRF analogues are being sought. One such product is TH-9507, being developed by the Canadian biotech company Theratechnologies. It is based on the natural hormone, but a trans-hex-3-enyl moiety has been added at the N-terminus, which increased its stability and half-life in the body.
The drug's safety, efficacy and pharmacokinetics were investigated in a Phase I trial in 60 health male volunteers aged between 50 and 60.1 They were given 0.5, 1 or 2mg of the drug or placebo subcutaneously once a day for seven days in a randomised, double blind trial. TH-9507 gave dose-related increases in growth hormone in the two lower doses; levels were similar in those given 1 and 2mg doses. Only minor side-effects were reported, including headache and reactions at the injection site. These were not related to dose.
Its efficacy was evaluated in a multicentre, randomised, placebo-controlled trial in 61 patients with HIV infection and abdominal fat accumulation.2 Subjects were given 1 or 2mg of the product or placebo subcutaneously once a day for 12 weeks. While 13 patients discontinued, the rates were similar for both drug and placebo groups. Significant average reductions in abdominal fat - 9.2% - were seen in those given the higher dose, while those on placebo had a small increase of 0.8%. No significant changes in limb or subcutaneous fat were seen, but lean body mass increased in all those patients given the active.
Various other Phase II trials have been carried out in patients with lipodystrophy resulting from a number of causes, such as the elderly and those with Type II diabetes. It is now undergoing Phase III studies in patients with HIV-associated lipodystrophy.