Hexadecapeptide AOD9604 [hGH]

[Michael Scally MD]

[AOD9604 is a synthetic fragment of hGH consisting of the amino acid residues 177–191. In obese Zucker rats, daily treatment for 19 days reduced over 50% body weight gain of the animals in comparison with the control. The adipose tissues of the AOD9604--treated animals were found to have an increase in lipolytic activity. In contrast to chronic treatment with intact hGH, chronic treatment with AOD9604 showed no adverse effect on insulin sensitivity of the animals, as demonstrated with euglycemic clamp techniques. The results suggest that the analogue of the hGH lipolytic domain may have the potential to be developed into an orally usable and safe therapeutic agent for obesity.]


Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J. Endocrinol. Metab. 2013;3:7. http://www.jofem.org/index.php/jofem/article/view/157/194

Background: The human growth hormone (hGH) has properties making it a potential candidate to treat obesity, however safety issues limit its long-term use.

AOD9604 is a peptide fragment of the C-terminus of hGH (Tyr-hGH177-191), which harbors the fat reducing activity of hGH, without its negative effects. In this paper the safety data of AOD9604 obtained in clinical trials are summarized.

Methods: Six randomized, double-blind, placebo-controlled trials were performed with AOD9604. Special focus was given to undesired effects associated with hGH treatment: increases in IGF-1 levels, insulin resistance, and impaired glucose tolerance. Blood samples were analyzed for presence of anti-AOD9604 antibodies to exclude immunogenicity.

Results: AOD9604 had no effect on serum IGF-1 levels, which confirms the hypothesis that AOD9604 does not act via IGF-1.

Results of oral glucose tolerance test demonstrated that, in contrast with hGH, AOD9604 has no negative effect on carbohydrate metabolism. There were no anti-AOD9604 antibodies detected in any of the patients selected for antibody assay. In none of the studies did a withdrawal or serious adverse event occur related to intake of AOD9604.

Conclusion: AOD9604 displayed a very good safety and tolerability profile indistinguishable from placebo. AOD9604 did not result in any of the adverse effects associated with full-length hGH treatment.

 

[Michael Scally MD]

Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology 2001;142(12):5182-9. http://press.endocrine.org/doi/full/10.1210/endo.142.12.8522

Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice.

One mechanism by which this may occur is through an interaction with the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-AR).

Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression of beta(3)-AR RNA, the major lipolytic receptor found in fat cells.

Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in the beta(3)-AR knock-out mice.

In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.

 

[Millard]

AOD-9604 was one of the main peptides at the center of the recent Australian doping scandal and the so-called "blackest day in Australian sport".

 

[Michael Scally MD]

AOD-9604 was one of the main peptides at the center of the recent Australian doping scandal and the so-called "blackest day in Australian sport".

Drug in Essendon case, AOD-9604, was banned
http://www.theaustralian.com.au/spo...-9604-was-banned/story-fnca0u4y-1226680951782

ALMOST six months after its report that rocked the nation's sport, the Australian Crime Commission now recognises a key drug in the current investigation into Essendon was banned at the time under the World Anti-Doping Agency code.