BAR HARBOR – The key to treating fibrodysplasia ossificans progressiva may be swimming around in the chilly Atlantic Ocean just outside Emma Albee’s back door.
In 1993, scientists at the Mount Desert Island Biological Laboratory discovered a natural antibiotic that may be the anxiously awaited cure for the FOP disorder and several types of cancer. It is called squalamine for the spiny dogfish, Squalus acanthias, from which it is derived.
“It could be the wonder drug,” said Dr. Michael Zasloff, a researcher with the University of Pennsylvania Medical Center and one of squalamine’s discoverers.
In the early 1990s, Zasloff was lecturing about his discovery of a type of antibiotic created inside animal cells, which he called magainins.
Noting the resistance to infection exhibited by a type of African tree frog, he surmised that the frog’s cells contained an antibiotic substance.
“This led to sort of a ‘gee whiz,’ which led to a realization,” Zasloff said. “Up to that point, people believed that powerful antibiotics were made by bacterias or molds, not animals.”
Zasloff published his findings in 1986 and became the darling of global medical media. He formed a research firm, Magainin Pharmaceuticals, and began searching for other antibiotic substances. Zasloff was swamped with calls from scientists suggesting that he consider their favored species.
Among the throng was Dr. John Forrest, a researcher at Yale Medical School and current scientific director of the Mount Desert Island Biological Laboratory. Forrest sought out Zasloff after a lecture to describe the hardiness of the spiny dogfish, a small shark native to the Atlantic coast.
“Sharks seem to heal very quickly,” Forrest said. “You can cut the skin of a shark, repair it with simple sutures, and it won’t get infected.”
And a dogfish embryo lives for two full years inside its mother’s body, swimming in uteruslike pouches that the dogfish flushes with unfiltered seawater.
“You know how delicate and sensitive a human fetus is, but the shark doesn’t seem to care,” Zasloff said. “The baby is in no way afraid of infection from the outside.”
He traveled to the lab in Salisbury Cove that summer.
Forrest and Zasloff harvested the stomachs and livers from hundreds of dogfish, which they boiled in vinegar to render the mysterious white substance that seemed to exhibit antibiotic properties.
“It turned out to be a totally new substance never before found in nature,” Forrest said.
Zasloff returned to his lab in Pennsylvania where he began investigating squalamine’s composition and properties.
On a whim, Zasloff sent a sample of squalamine to a colleague familiar with angiogenesis inhibitors – rare substances that inhibit the growth of blood vessels. Though a ho-hum antibiotic, squalamine is one of the most potent angiogenesis inhibitors known.
“Magainin is a wimp,” Zasloff told The New York Times.
But the scientific community was slow to embrace squalamine’s new identity.
“It’s like you’re in a dog show, and you suddenly announce that you have a horse,” Zasloff said. “There was a certain amount of re-education necessary.”
Squalamine suddenly was poised as a miracle cure, a substance with the ability to stop the blood flow that feeds many cancerous tumors – and the FOP lesions of patients Zasloff had been studying for decades. Without a constant nutrient supply, the tumor or lesion stops growing and begins to recede.
Zasloff’s lab developed a means of synthesizing squalamine from a soybean hormone and subjected it to a slew of tests. In animals, squalamine was shown to dramatically reduce tumors when used in conjunction with chemotherapy.
Today, squalamine is navigating the five- to 10-year Food and Drug Administration approval process, jumping through hoops and competing with a handful of other promising angiogenesis inhibitors. “It’s in a beauty contest,” Zasloff said.
In 1997, the FDA deemed squalamine safe for human use. A few weeks ago, a human trial proved squalamine’s effectiveness for treating lung cancer. Squalamine could be marketed for cancer treatment within the next two years, Zasloff said.
Zasloff expects to begin testing squalamine’s effectiveness on the lesions of children with FOP early in 2001. He hypothesizes that squalamine given intravenously within the first few days of a lesion’s emergence will prevent bone growth. Squalamine could even make the surgical removal of excess bone a possibility.
“Within the next three months, we’ll begin treating children – as many as we can get,” he said. That would be welcome news for families fighting the disorder.
“We feel lucky that Emma was diagnosed with FOP at a time when it seemed as though just around the corner, there would be a treatment,” said Emma’s mom, Patti Pinkham.
Considering the possibility in a small shark swimming in the waters off Seal Cove, Pinkham just may be right.
To help finance the search for a treatment, contact the International FOP Association at P.O. Box 196217, Winter Springs, Fla., 32719-6217; (407) 365-3213; e-mail: firstname.lastname@example.org.