Shark Compound Has Potential to Treat Human Viruses
September 19, 2011 – A compound initially isolated from dogfish sharks shows potential as a broad-spectrum human antiviral agent, according to a study led by a Georgetown University Medical Center (GUMC) investigator.
The GUMC findings were reported in the Proceedings of the National Academy of Sciences Early Edition online today.
The compound squalamine, which since 1995 has been synthesized in a process not involving natural shark tissue, has been tested for the treatment of cancer and several eye disorders.
But in both lab and animal experiments, the compound effectively demonstrated antiviral activity against viruses ranging from dengue and yellow fever to hepatitis B, C, and D.
“To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people,” says the study’s lead GUMC investigator, Dr. Michael Zasloff.
The doctor also may have answered the longstanding mystery of how sharks, which have a very primitive immune system, effectively fight the viruses that plague all other living creatures.
“I believe squalamine is one of a family of related compounds that protects sharks and some other ‘primitive’ ocean vertebrates, such as the sea lamprey, from viruses,” says Zasloff, professor of surgery and pediatrics and scientific director of the Georgetown Transplant Institute.
The doctor says researchers may be able to harness the shark’s immune system to turn antiviral compounds into agents that protect people against such viruses.
“That would be revolutionary,” he says. “While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active.”
Zasloff discovered squalamine in 1993 when he was a professor of pediatrics and genetics at the University of Pennsylvania searching for novel antibacterial agents.
“I was interested in sharks because of their seemingly primitive but effective immune system. No one could explain why the shark was so hardy,” he says.
The investigator later found that squalamine inhibited the growth of rapidly growing blood vessels, such as those found in tumor growth and certain retinal diseases such as macular degeneration and diabetic retinopathy.
Squalamine was subsequently tested in these conditions, and some of those clinical trials are ongoing.
In animal studies, his collaborators discovered that squalamine controlled infections of yellow fever, Eastern equine encephalitis virus, and murine cytomegalovirus, and in some cases cured the animals.
“We have not yet optimized squalamine dosing in any of the animal models we have studied and as yet we do not know the maximum protective or therapeutic benefit that can be achieved in these systems,” Zasloff says. “But we are sufficiently convinced of the promise of squalamine as an antiviral agent that we intend to take this compound into humans.”
Zasloff is the inventor on a patent application that has been filed related to the technology described in his paper.