Natural Substance Squalamine Shows Promise as Treatment for Parkinson’s

Natural Substance Squalamine Shows Promise as Treatment for Parkinson’s

Squalamine, a natural product known for its cancer- and infection-fighting qualities, has shown promise as a treatment for Parkinson’s disease, according to preliminary results of a new study.

The research, “A Natural Product Inhibits The Initiation Of α-Synuclein Aggregation And Suppresses Its Toxicity,” was published in the journal Proceedings of The National Academy of Sciences.

Parkinson’s develops when alpha-synuclein abnormally aggregates in neurons. Under normal conditions, the protein helps maintain signaling and communication between neurons.

In Parkinson’s, alpha-synuclein aggregates into structures known as Lewy bodies, which disrupt neuronal communication and lead to movement problems.

Squalamine is a steroid molecule found in dogfish sharks that has served as a template for a safer, synthetic treatment that can be used in research.

The compound inhibits the formation of alpha-synuclein aggregates and protects neurons against their toxicity. Using cell cultures, researchers found that squalamine competes with alpha-synuclein for access to binding sites in the vesicles, bubble-like structures that carry molecules from one neuron to another, allowing communication.

This propensity reduces the chance that alpha-synuclein will aggregate and clump vesicle transport. Further analyses showed that squalamine reduced the toxicity of the aggregates.

“To our surprise, we found evidence that squalamine not only slows down the formation of the toxins associated with Parkinson’s disease, but also makes them less toxic altogether,” Christopher Dobson, senior author of the study, said in a news release.

Researchers also used laboratory worms (C.elegans) that were genetically modified to express high amounts of alpha-synuclein in their muscle cells. When alpha-synuclein aggregates began to form, the worms lost movement. However, treatment with squalamine prevented this loss.

“We could literally see that the oral treatment of squalamine did not allow alpha-synuclein to cluster, and prevented muscular paralysis inside the worms,” said Michael Zasloff, another study author.

There is a long road ahead before squalamine can become a Parkinson’s treatment, but the preliminary results are promising. Researchers are designing a clinical trial to test squalamine in Americans with Parkinson’s.

Future studies are necessary to address such questions as what benefits squalamine can offer, what form of treatment it should take, and whether it could cross the blood-brain barrier and reach the brain. It is also necessary to understand whether blocking the aggregation of alpha-synuclein would produce side effects, because the protein plays an important role in healthy neurons.

“In many ways squalamine gives us a lead rather than a definitive treatment,” Dobson said. “Parkinson’s Disease has many symptoms, and we hope that either this compound, or a derivative of it with a similar mechanism of action, could alleviate at least some of them.

“One of the most exciting prospects is that, subject to further tests, we might be able to use it to make improvements to patients’ lives, while also studying other compounds with the aim of developing a more powerful treatment in the future.”


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