Merck and C Sixty to pursue fullerene antioxidant technology - In the field: pharmaceutical science & technology news

Merck and Co. (Whitehouse Station, NJ) has entered into an agreement with the biotechnology company C Sixty (Houston, TX) for the development and commercialization of C Sixty's fullerene antioxidant technology. Although the two therapeutic areas covered by the agreement have not been released, fullerenes have shown therapeutic antioxidant potential in several areas, including neurogenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease), cardiovascular diseases, skin conditions, and the aging process.

A fullerene is a natural hollow sphere composed of 60 carbon atoms. Discovered in 1985, these molecules were named after Buckminster Fuller because their shape resembles the geodesic dome that Fuller invented. "Fullerenes have interesting and unique electrochemical properties that make them very useful" notes Russ Liebovitz, vice-president of research and development at C Sixty.

Those properties include an external electron cloud that makes it easy for the fullerene to pick up electrons and stabilize free radicals. "That means fullerenes have the potential to serve as very powerful antioxidants, by interacting with a wide variety of oxygen free radicals that cause extensive damage and are responsible for a number of diseases and the aging process," he continues.

Under normal circumstances, the body's endogenous antioxidants can accommodate the small quantities of free radicals produced in normal biological processes. In certain disease states, however, free radicals are overproduced. These unstable molecules, which have an unpaired electron, react with other molecules and can start a chain reaction of damage. For example, one free radical may react with a molecule in a cell membrane, damaging it and generating another free radical in the process. The new free radical can react with other cell structures, causing more damage, and so on. Antioxidants can stop the damage by taking up those free electrons and stabilizing them. "Fullerenes do this more effectively than almost anything else looked at," Liebovitz says.

Formulating the molecules

The fullerenes are highly insoluble, a characteristic that must be addressed before their power can be harnessed. This has been the primary focus of C Sixty's development work. "We can attach groups to the surface of fullerenes that make them more soluble in water, blood, and many biological membranes. This allows them to get to the site where antioxidant activity occurs," says Liebovitz.

If targeted to the right sites, fullerenes can stop the production of free radicals at their source. "Since one free radical can damage hundreds or thousands of molecules" notes Liebovitz, "it's a hundred or a thousand times more effective to inactivate the free radical where it's produced rather than at one of the thousand sites it's damaging downstream."

So far, C Sixty hasn't faced any serious issues regarding the stability of the adapted molecules. "We might have three or four formulations that go to a specific organ or target within those organs," Liebovitz says, "so obviously we'll pick the ones that have the best profile with respect to pharmacokinetics."

The Merck-C Sixty partnership

Under the terms of the agreement between Merck and C Sixty, Merck has the exclusive right to conduct research on fullerenes in two undisclosed therapeutic areas. If Merck decides to move forward with the technology, Merck can exercise its commercial license option to market the drugs, which can be supplied by C Sixty.

"Getting a new class of molecules, no matter how powerful, through the regulatory process and through the barriers associated with marketing is a formidable task," comments Liebovitz. "We think we can be more effective by partnering with a company like Merck that has experience doing this."

Scale-up

Currently, C Sixty is producing small quantities of the modified fullerenes at its facilities in Houston, Texas, using core fullerenes produced by various suppliers in North America, Japan, and other parts of the world. Liebovitz is confident that fullerene production capacity is sufficient to meet future demand as well. "Three years ago, the world's capacity to produce fullerenes would not have been sufficient to produce the quantities of drug needed for any single indication" Liebovitz points out. "But the fullerene suppliers of the world have been one step ahead of us and have expanded their capacity exponentially." As for the ultimate production of the final drug products in commercial quantities, Liebovitz says that C Sixty and Merck will determine the most efficient and cost effective way to produce them, whether that means building new production facilities or outsourcing.