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.
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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."