Shark-Derived Compound May Treat Parkinson's Disease

Squalamine was seen to inhibit α-synuclein and associated toxicities in models of Parkinson’s disease.

Findings from a recent study suggest that a chemical compound derived from sharks may effectively treat Parkinson’s disease.

In the study, which was published by the Proceedings of the National Academy of Sciences, the authors discovered that squalamine derived from dogfish sharks reduced the creation of α-synuclein, which is characteristic of Parkinson’s disease. These results were seen in both roundworm models of Parkinson’s disease and in human neuron cells.

Parkinson’s disease is characterized by tremors, limb stiffness, and problems with movement and balance. Approximately 60,000 individuals are diagnosed with the disease each year in the United States.

While the exact cause of Parkinson’s disease is still unknown, other studies have shown that a build-up of α-synuclein may trigger the condition. Similar to Alzheimer’s disease, α-synuclein forms clumps in the brain of patients with Parkinson’s disease, which leads to cell death, according to the study.

The investigators believe that squalamine could potentially block the creation of α-synuclein clumps in the brain, and prevent brain cell death. Squalamine has shown strong antimicrobial properties in previous studies.

In the new study, the researchers aimed to determine whether squalamine could affect the aggregation of α-synuclein in the brain.

First, squalamine was tested in in vitro models to establish how it interacts with α-synuclein and lipid vesicles, which are known to cause a build-up of the protein in brain cells. The investigators found that squalamine successfully inhibited protein aggregation by stopping α-synuclein from binding to negatively charged lipid vesicles.

The authors then introduced squalamine to human neuronal cells that were exposed to α-synuclein aggregates. The investigators discovered that squalamine inhibited protein aggregates from binding to brain cell membranes. This prevented toxicity that is seen in Parkinson’s disease.

Squalamine was then tested in Caenorhabditis elegans, which are an ideal model because they share approximately 40% of their genes with humans. These C. elegans were modified to have increased α-synuclein expression in muscle cells, which would eventually lead to paralysis during development, according to the study.

When the C. elegans were administered squalamine orally, the authors discovered that the shark-derived compound inhibited α-synuclein aggregates and prevented the toxic effects of the protein.

"We could literally see that the oral treatment of squalamine did not allow α-synuclein to cluster, and prevented muscular paralysis inside the worms,” said study co-author Michael Zasloff, MD, PhD.

The investigators believe their findings show that squalamine may be an effective way to prevent α-synuclein aggregates. They are currently in the process of creating a clinical trial to test the compound in patients with Parkinson’s disease, according to the study.

However, the researchers said that future studies should be conducted to determine whether squalamine can target the parts of the brain that are prone to by α-synuclein build-up. Regardless, the investigators believe that this compound could offer numerous benefits.

"Targeting alpha-synuclein in the gut may perhaps in some cases be sufficient to delay the progress of other aspects of Parkinson's disease, at least for symptoms concerning the peripheral nervous system," concluded study co-author Michele Vendruscolo, PhD.