Parkinson's-Fighting Steroid Is Identified in Fast Food Fish
The spiny dogfish shark carries a potent toxin-fighting steroid, which scientists can now manufacture synthetically.
The spiny dogfish shark, which has been marketed as "rock salmon" and reportedly sold as a fast food fish, turns out to carry a potent toxin-fighting steroid that shows promise in treating Parkinson's and a certain form of dementia, new research finds.
Concerns over fast food and fishing of the shark, which is now listed as being vulnerable to extinction by the IUCN, have been erased since scientists have synthesized the steroid—squalamine—in a lab, so no spiny dogfish sharks have to die in order for people to benefit from the compound.
Results of the new research on squalamine, conducted by an international team, are reported in the Proceedings of the National Academy of Sciences.
"The synthesized steroid is identical to the molecule produced in the shark," co-senior author Michael Zasloff told Seeker. "It is a beautiful white powder. It will be administered as an oral tablet in human clinical trials."
Zasloff, a professor of surgery and pediatrics at Georgetown University School of Medicine, and a scientific director of the MedStar Georgetown Transplant Institute, has been studying the spiny dogfish shark for well over two decades. The shark may live up to 100 years, and is suspected of having the longest known gestation period of animal: 18 to 24 months.
One reason for the longevity is that "the shark is remarkably resistant to infections, despite having a primitive immune system," Zasloff said. "We suspected that this animal made protective compounds."
In earlier research, he and his colleagues discovered squalamine in the shark and determined that the steroid had antimicrobial properties. The researchers then determined its chemical structure and devised a way to synthesize it from a plant steroid.
For the new study, lead author Michele Perni, Zasloff and their team genetically programmed nematode worms (C. elegans is a popular animal model for research projects) to over-express a protein called alpha-synuclein. Clustering of this protein happens with Parkinson's as well as with Lewy Body Dementia, a condition said to have afflicted the late entertainer Robin Williams.
Photo: Spiny dogfish shark. Credit: Doug Costa, NOAA/SBNMS
Zasloff explained that alpha-synuclein is attracted to negatively charged cellular surfaces. Squalamine, a positively-charged molecule, is attracted to these very same surfaces, such as within nerve cells.
For people with Parkinson's, tiny vesicles positioned at nerve endings become coated with the protein, so they can start to aggregate with others and clump together. As the clumps grow, the nerve's function becomes damaged, often leading to the death of the entire cell.
The scientists showed that squalamine can displace the damaging protein from nerve cells. Even if some minor clumps form, Zasloff said, "The normal cell has a means of naturally digesting these aggregates, and can do so effectively, so long as the garbage disposal system isn't overwhelmed."
That's exactly what happened to the nematode worms. Those not given squalamine experienced cellular damage and became paralyzed, but the treated worms were able to stave off the protein clustering and resulting problems.
You might be wondering why a shark that doesn't suffer from Parkinson's and/or dementia would produce squalamine. Zasloff said the steroid "can kill bacteria, fungi, parasites and viruses," so it "protects the shark from the infective agents that must accompany the food it ingests."
The connection to humans may not be so remote. Intriguingly, most people with Parkinson's suffer from severe constipation and other gastrointestinal problems, with such symptoms often appearing before the obvious onset of the disease. As a result, Zasloff said, "Many in the field now believe that Parkinson's actually begins in the gut." Lewy Body Dementia may initiate in a similar manner, since Lewy bodies—the abnormal protein aggregates—can be found in the gut.
The planned multi-center clinical trial on humans will focus on how squalamine affects GI function, and how this, in turn, may link to disease formation.
It's important to note that "drugs" and nutritional supplements on the market now under the label "squalamine" do not contain any significant amounts of the steroid, according to Zasloff.
"The amount of squalamine in shark tissues is quite low," he explained, "even in the liver of the dogfish. I do worry that the Asian fisheries will respond to our report by further decimating shark species."
An actual squalamine-based drug, made from the synthesized compound, is already being envisioned.
Co-author Christopher Dobson explained that if the forthcoming trials on humans are successful, "it is possible that a drug treating at least some of the symptoms of Parkinson's Disease could be developed from squalamine.
We might then be able to improve on that incrementally, by searching for better molecules that augment its effects."
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