Dogfish Shark Steroid Attacks Parkinson’s Toxin

A synthesized steroid mirroring one naturally made by the dogfish shark prevents the buildup of a lethal protein implicated in some neurodegenerative diseases, reports an international research team studying an animal model of Parkinson’s disease. The clustering of this protein, alpha-synuclein, is the hallmark of Parkinson’s and dementia with Lewy bodies, suggesting a new potential compound for therapeutic research.

The pre-clinical study results show that the synthesized steroid, squalamine, prevents and eliminates alpha-synuclein build-up inside neurons by unsticking the protein from the inner wall of nerve cells, where it clings and clusters into toxic clumps, researchers say.

The animal model used for this study is a nematode worm genetically engineered to produce human alphasynuclein in its muscles. As the worms age, alphasynuclein builds up within their muscle cells, causing cell damage and paralysis.

“We could literally see that squalamine, given orally to the worms, did not allow alpha-synuclein to cluster, and prevented muscular paralysis inside the worms,” says the study’s co-senior author, Michael Zasloff, MD, PhD, professor of surgery and pediatrics at Georgetown University School of Medicine and scientific director of the MedStar Georgetown Transplant Institute.

Zasloff, an expert in innate immune systems, has been studying squalamine for more than 20 years. He discovered it in dogfish sharks in 1993 and synthesized it in 1995 in a process that does not involve use of any natural shark tissue. His research, as well as that by other scientists, has established antiviral and anticancer properties of the compound. This is the first study to show it has neurological benefits in in vivo models of Parkinson’s.

Zasloff says a clinical trial with squalamine in Parkinson’s disease is being planned. “Squalamine could be especially suited to work in the gut with the goal of treating the gastrointestinal symptoms of Parkinson’s,” he adds.