BIO profile: Beta agonists for metabolic modification

The use of antibiotics as growth agents in livestock is increasingly concerning both the meat industry and regulatory bodies, mainly because of the possible link to antibiotic resistance. McDonalds has banned the use of antibiotics in the production of beef for its hamburgers and where the golden arches go, most are likely to follow.

This movement has opened up the market for other compounds that promote muscle growth and reduce fat in livestock. West Australian company Stirling Products hopes to step into that breach, developing a beta agonist that shows improved muscle production and reduced fat production, perfect not only as a growth agent for livestock but to tackle the growing phenomenon - pardon the pun - of obesity in companion animals.

Stirling Products' main compound is R-salbutamol, a purified version of salbutamol (known as albuterol in the US), which is the active compound in asthma medication. Salbutamol is a racemic or mixed compound, containing two isomers - R and S. The chemical structures of these isomers are identical but they have different levels of activity.

Justin Stillitano, Stirling's recently appointed business development manager, says the company purifies the compound and isolates the R isomer, which is receptor specific and chemically pure, meaning less of the drug needs to be used to attain the desired effect and it reduces undesirable side-effects due to the absence of the unwanted isomer.

"In the airways, R-salbutamol is a bronchodilator and affects smooth muscle, thereby opening the lungs and allowing air to passage," Stillitano says. "Technically, R-salbutamol is a beta 2 receptor agonist, the same receptor that adrenaline binds to in the body. When R-salbutamol is administered to animals, it stimulates the beta 2 receptor, which in turn repartitions energy. In other words, energy that is destined for fat production is reprogrammed to muscle production.

"This repartitioning effect, which decreases fat production but stimulates muscle production, has benefits to animals in a number of applications such as growth promotion in livestock and treating obesity in companion animals."

Stirling Products has three applications for R-salbutamol in animals, he says. "Firstly as a growth agent across all livestock species - cattle, sheep, chicken and pigs. When R-salbutamol is added to the feed of livestock, not only does it increase their growth rate and optimise their food utilisation, but it also produces a carcass with less fat and more lean meat. This means a greater return for producers and a healthier product for consumers.

"The second application for the technology is as a treatment for obesity in companion animals. Up to 35 per cent of household dogs and cats are obese and the rate of obesity in these animals is growing at similar rates to humans. In initial trials with genetically obese rats, we observed a 79 per cent reduction in weight gain." Stirling is completing a trial in obese dogs and hopes to report its results shortly.

The third application is heaves in horses. Heaves, or recurrent airways obstruction (RAO), is a respiratory disorder in which the animals develop asthma-like symptoms when over-exercised or when exposed to certain environmental stimulates such as pollens.

"This is a more traditional application for R-salbutamol as it is used in a similar application in humans today," Stillitano says. "Currently no horse-specific aerosol is available to treat heaves. Stirling has set up a partnership in Europe, Pulmovet ApS, to further the commercialisation of this application."

Results to date

Stirling has also filed and received Investigational New Drug application numbers for swine, chickens, companion dogs, heaves in horses and sheep.

"Trials conducted to date have shown significant production gains in swine, poultry, cattle and sheep," Stillitano says. "For example, in one swine trial, a 21 per cent improvement in feed efficiency was achieved and a further trial in broiler chickens produced almost a 30 per cent reduction in fat with an 11 per cent increase in lean meat."

It has also commenced several new trials, including a dose confirmation study in pigs and one in farmed fish, measuring the production gains in barramundi. "Aquaculture is a huge market for growth agents. Natural fish supplies are decreasing and more and more countries are developing farmed fish markets. We expect results of our trials in the second quarter of 2007."

The company also has a number of partners, including South African company Afgri for trials in swine, one with global animal health company Merial in sheep and a recent memorandum of understanding with Canadian company Progressive BioActives.

"Our current agreement with Merial allows them to conduct field trials with R-salbutamol in sheep concurrently with some proprietary technology they have to deliver the drug," he says. "Successful results could ultimately lead to a global licensing arrangement for the supply, manufacture and distribution of the resulting product.

"Progressive BioActives or PBI is a Canadian company that has developed natural compounds from the cell wall of yeast that are designed to boost the immune system of livestock. As these products are natural, the time it takes to register these types of products with regulatory agents around the world is relatively short."

History

Still a relatively new company, Stirling Products listed on the stock exchange early in 2004. The initial founders, who are no longer with the company, obtained the foundation intellectual property from Florida-based Bridge Pharma. The company later purchased the intellectual property outright, and the original patent holder, Dr Gunnar Aburg, is now both a director and significant shareholder in the company.

The company is led by Dr Calvin London, a veterinary microbiologist who has specialised in gut and skin microbes. He has worked in the pharmaceutical industry for 30 years, including stints with the Upjohn company, Pharmacia Upjohn, Schein Pharmaceuticals and INO Therapeutics.

The market for obese companion animals is obviously expanding - pardon the pun again - with Pfizer recently having a companion animal obesity drug, Slentrol, approved by the FDA. It is expected to be released on the market shortly.

"This drug has a different mechanism of action to R-salbutamol and focuses more on reducing how much food animals eat rather than repartitioning the energy consumed away from fat production," Stillitano says.

"R-salbutamol transfers energy destined for fat production to other processes in the body. So when an obese animal has R-salbutamol administered, the animal will become more lean and ultimately lose weight.

Stirling is strategically focused on animal health, although there is the obvious potential for use in human health, obesity in particular.

"To find a cure, that magic pill for humans which will cure obesity, is considered the Holy Grail for major pharmaceutical companies," Stillitano says. "If we see that R-salbutamol is a success in the companion animal market we will definitely explore its potential use in humans.

"However, to get any drug approved for human use is very capital-intense so it is more likely we will find a partner who can develop this application for us."

Stirling Products is exhibiting with other WA companies, research departments and the state government on the Australian pavilion at BIO 2007.