Obesity is the Western World’s most common health problem, and has reached epidemic proportions according to the World Health Organisation. More than 20% of the adult population in developed countries are obese – more than 300 million adults worldwide. In addition, more than 50% of adults in developed countries are overweight. Obesity is associated with other health-related problems such as heart disease, cancer and diabetes.
We found that osteoarthritic rabbits administered intra-articular AOD9604 injections had better outcomes with lesser morphological and histolopathological damage than was observed in the control group. AOD9604 is a disulphide-constrained peptide that comprises 15 amino acids from the C-terminal sequence of human GH and an additional N-terminal tyrosine residue: YLRIVQCRSVEGSCGF . The exact mechanism underlying the action of GH in OA is unknown. Previous studies have shown that GH can act directly on the growth plate by stimulating local production of IGF-1 and by increasing cartilage metabolism [9,16] and chondrocyte proliferation . Although AOD9604 is not a high-affinity agonist of the GH receptor and does not stimulate the proliferation of cells transfected with the GH receptor, it retains some functions of GH . Initially, AOD9604 was investigated for the treatment of obesity in humans. In rodent models of obesity, AOD9604 showed a similar effect of weight loss as that observed with GH . However, AOD9604 does not induce diabetes and does not stimulate the production of IGF-1 .
The evidence so far suggests that there may be some effect on cartilage and bone densities, and it is correlated with weight loss. I understand that there is no evidence to suggest that it stimulates the release of IGF-1, which is the mechanism via which growth hormone gets most of its purported performance enhancing effects (i.e. muscle bulk). Whilst this is a decent list of things to test if one is considering AOD9604 as simply a variant of growth hormone, it is by no means exhaustive of all the mechanisms via which a drug can enhance athletic performance. The evidence thus far suggests that AOD9604 could be performance enhancing, but there is nothing I would hang my hat on. That is why I maintain that Dank is more sorcerer than scientist.
Peptides are not to be confused with synthetic human growth hormone drugs, which are injected into the bloodstream to provide rapid results. HGH is said to be Hollywood's secret weapon, with top stars, filmmakers and studio execs hooked on the youthful effects, but synthetic hGH is tightly regulated in Australia and verboten unless there's a proven growth hormone deficiency (most cases are in children).
A total of 18 patients (3.6%) reported at least one SAE. The distribution of SAEs was similar among all treatment groups (Table 2). The most common SAEs reported were in the injury, poisoning and procedural complications body system class (6 patients, 1.2%). The others were general disorders and administration site conditions (2 patients; 0.4%), infections and infestations (2 patients; 0.4%), musculo-skeletal and connective tissue disorders (2 patients; 0.4%), and vascular disorders (2 patients; 0.4%).
The test substance was either administered intravenously (studies METAOD001 and METAOD002) or as a capsule/tablet. The hexadecapeptide AOD9604 was produced under cGMP conditions by PolyPeptide Laboratories (Torrance, CA, USA). For studies 1 and 2, the product was supplied in a lyophilized form and reconstituted before usage with the designated volume of sterile water for intravenous injection. The capsules/tablets were manufactured using a common excipient mix (Capsules: Mannitol, PEG3350 (in studies METAOD003, METAOD004 and METAOD005)); or Tablets: L-Arginine Free Base, Microcrystalline Cellulose, Fumed silica, Magnesium Stearate (in study METAOD006)).
There were no changes in laboratory parameters or vital signs in any treatment group. There were no clinically significant abnormalities in vital signs, safety tests, or ECGs during the studies. At no time were statistically significant differences in IGF-1 levels among the treatment groups and placebo detected. The overall mean changes in IGF-1 were 1.76 nmol/L and 1.24 nmol/L after 12 and 24 weeks of treatment, respectively. There were no statistically significant differences between the treatment groups or placebo (P = 0.50844 after 12 weeks and P = 0.75754 after 24 weeks).
Background: The human growth hormone (hGH) has fat loss properties making it a potential candidate to treat obesity. AOD 9604 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 AOD 9604 obtained in clinical trials are summarized.
Hexarelin: Part of a family of drugs called growth hormone-releasing peptides (GHRP; commonly shortened in media to “peptides”) Hexarelin increases the body’s production of its own human growth hormone, and in so doing may help increase muscle mass and strength. The potential adverse effects of repeated doses of peptides may include various hormonal imbalances in the body. Hexarelin is banned by WADA. –– Benjamin Koh
The effect of a single daily ip dose of saline, AOD9604, or hGH on body weight changes in lean male C57BL/6J (A) or obese (ob/ob) mice (B) for 14 d. Caloric intake was recorded every second day and presented as an average for each day in lean (C) and obese (D) mice. Results are expressed as the mean ± SE of six animals in each group. *, P< 0.01; #, P < 0.05, compared with saline.
Experimental animals were anesthetized with an intramuscular injection of xylazine (Rompun®; Bayer Co., Seoul, Korea) at a dose of 1.9 mg/kg and ketamine (Ketar®; Yuhan Co., Seoul, Korea) at a dose of 46 mg/kg. The right knee joints of all rabbits were shaved and sterilized. Then, 2 mg of collagenase type II from Clostridium histolyticum (Sigma Co., St. Louis, MO, USA) was prepared for intra-articular injection. Collagenase was dissolved in a sterile phosphate buffered saline (pH 7.4) and filtered with a 0.22-μm membrane. The solution was slowly injected into the right knee joint using ultrasound guidance. The same injection was repeated 3 days after the first injection, as previously reported (Figure 1) .
ASADA gave advice to the ACC, and perhaps Essendon, that AOD-9604 was not banned under the S2 category. Given the expectation that AOD-9604 would not be anabolic because it lacked the ''anabolic region'' of HGH, it is perhaps understandable that ASADA did not classify it under S2 in 2011 and 2012, although its close structural relationship to the banned HGH should have been sufficient to include it on the banned list.