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Deep Sea Treatment for Superbug Holds Promise, Comes With Challenges

Scientists have long suspected that the sea holds the potential to provide new medicines for a variety of human ailments and diseases.

In recent years, researchers have begun to gain a greater understanding about its potential in fighting antibiotic-resistant infections such as the headline-grabbing methicillin-resistant Staphylococcus aureus, or MRSA. The so-called superbug has proven to be particularly difficult to treat and thrives in hospitals, where patients with weakened immune systems and open wounds are at greater risk for infection.

A group of United Kingdom scientists recently discovered a bacterium found in Japanese seabeds with the ability to kill MRSA. The new species produces a unique antibiotic that has the potential to one day treat humans.

But few marine-derived natural products are currently on the market or in clinical trials.

Scientists pointed to a lack of interest on the part of the pharmaceutical industry and challenges involved in forming companies around their ideas during the annual American Association of Pharmaceutical Scientists meeting held Nov. 11 to 15 at the San Diego Convention Center. The event attracted about 9,000 scientists and industry observers from a variety of disciplines.

“We were concerned that although the pharmaceutical industries explored terrestrial microorganisms for more than 60 years, they never approached the complexity of the world’s oceans,” said William Fenical, a pioneer of marine microbiology at the Scripps Institution of Oceanography and director of its research division, the Center for Marine Biotechnology and Biomedicine.

About half of all prescribed medicines are extracted or derived from terrestrial plants or microorganisms. But despite tremendous advances in medicine, many deadly diseases and crippling conditions remain without a cure.

MRSA has gained extra attention in recent months because of its rising rate of infection. The superbug was responsible for an estimated 94,000 life-threatening infections and 18,650 deaths in 2005, researchers at the Centers for Disease Control and Prevention reported this year.

“These superbugs headlined by MRSA formed the foundation of a medical emergency that may reach its peak in less than five years unless we understand how to ameliorate that problem,” Fenical said.


Bottom Of The Ocean

The search for an antibiotic on the bottom of the ocean makes sense to scientists because, they say, the sea-dwelling microorganisms haven’t come into contact with disease-forming bacteria on land. And their special living conditions and functions within the ocean’s ecosystem force them to produce a vast number of enzymes that have therapeutic benefits to humans.

But Fenical pointed to an “alarming trend” where approval ratings for new antibiotic drugs have diminished since the beginning of the 1990s. Today, he said, it’s not unusual to find about one new antibiotic approved each year.

“The pharmaceutical industries today have chosen to de-emphasize antibiotic discovery for economic reasons in part, but also because the traditional sources, the soil-derived microorganisms, are no longer forming the foundation of drug discovery in the pharmaceutical industry,” Fenical said. “So, antibiotic discovery has been almost totally curtailed in the major industries at a time when the incidence of drug resistance is rising now to 60 or 70 percent for MRSA.”

He said it is clear that scientists need to look elsewhere to discover new antibiotics with new structure types because they aren’t finding new breakthroughs on land. But finding enough money to support their research could prove challenging.

Gerold Lukowski, a German scientist with the Institute for Marine Biotechnology in Greifswald, Germany, said a microorganism at the bottom of the Baltic Sea showed resistance to MRSA in animal tests. The group developed a formulation around its discovery but said challenges lie ahead.

“It’s difficult to find a company that’s been able to bring it into the market,” he said.

At least one local company has been able to advance marine-derived drug candidates. Nereus Pharmaceuticals was formed around the idea of discovering cures at the ocean’s depths. Co-founded by Fenical with Forward Ventures partner Stan Fleming and President and Chief Executive Kobi Sethna, the privately-held company has focused much of its efforts on treating cancer.

Two of its cancer-fighting drug candidates derived from marine microbes are poised to enter into late-stage clinical trials by 2009.

The company’s discovery portfolio also includes additional drug candidates for oncology, infectious diseases and inflammation.

Nereus recently raised $45 million from the private placement of its preferred stock but has yet to garner interest from the pharmaceutical industry.

“Nereus has been able to generate an extraordinary pipeline of molecules based on limited experience,” Fleming said. “Unfortunately, that hasn’t gotten the attention of the pharmaceutical industry. It is, decidedly, not sexy.”

Part of the reason for the industry’s lack of interest might be attributed to its past. Previous findings in sea squirts and ocean plants proved difficult to work with in laboratories. Additionally, there weren’t enough of the organisms surviving in the wild to support the industry.

The pharmaceutical industry today has placed a great deal of attention on synthetic molecules, and Fleming said the industry sees the return to natural ingredients as a step backward.

He said, however, that the company has received significant interest in the industry with the molecules it has been able to produce.

“If they like the golden eggs, they might one day think about going back to buy the goose,” he said.

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