There are up to 1 million people in the United States living with Parkinson’s disease. About 60,000 people each year are diagnosed with the disease. Parkinson’s disease is a progressive condition characterized by movement problems, tremors, limb stiffness and problems with coordination and balance. It remains unclear what exactly causes Parkinson’s disease, but studies have shown that a buildup of the protein alpha-synuclein in the brain could contribute to its development. A new study published in the Proceedings of the National Academy of Sciences shows that a chemical compound found in dogfish sharks may be able to treat Parkinson’s disease.
The chemical compound is called squalamine, and it may be able to reduce the formation of toxic proteins associated with the development of Parkinson’s disease. The results of the study showed that in roundworm models of Parkinson’s disease and human neuronal cells, squalamine halted the toxicity and buildup of alpha-synuclein.
For the first step of the study, the researchers conducted several in vitro experiments to observe the way squalamine interacts with alpha-synuclein and lipid vesicles. According to previous studies, vesicles trigger the buildup of alpha-synuclein in neurons.The team found that by preventing the protein from binding to negatively charged lipid vesicles, squalamine was able to halt alpha-synuclein buildup. This is important because the negatively charged lipid vesicles are where alpha-synuclein aggregates usually form.
Then, the team applied squalamine to human neuronal cells, which had been exposed to pre-formed alpha-synuclein aggregates. They found that squalamine prevented alpha-synuclein aggregates from binding to the outer membrane of the cells, thus stopping the toxicity of the protein.
The next step of the experiment was testing squalamine on the roundworm Caenorhabditis elegans. This roundworm is an ideal experimental model for human disease because according to the first whole-genome sequencing study of Caenorhabditis elegans, these roundworms share at least 40 percent of their genes with humans. This makes them a useful experimental model for human disease. The researchers in this study genetically modified the Caenorhabditis elegans in order to overexpress alpha-synuclein in their muscle cells. This would lead them to become paralyzed as they developed. However, the researchers found that when they administered squalamine to the Caenorhabditis elegans orally, the compound stopped alpha-synuclein aggregates from forming.
This study may have a big impact on the way doctors treat Parkinson’s disease in the future. The researchers believe that this study suggests that the buildup of alpha-synuclein has the potential to be prevented using squalamine. The team is currently organizing a clinical trial to test the compound in people with Parkinson’s disease.
The team notes, however, that before squalamine can be considered a possible treatment for Parkinson’s disease, a number of questions should be addressed through future research. One unanswered question is whether squalamine can target areas of the brain that are susceptible to alpha-synuclein buildup when it is taken orally. However, researchers suggest that squalamine could offer benefits through the gut. Study co-author Professor Michele Vendruscolo says that targeting alpha-synuclein in the gut may be helpful in delaying the progress of other aspects of the disease, particularly for symptoms concerning the peripheral nervous system.
It will be interesting to see what future studies find. Hopefully, squalamine will one day be able to treat Parkinson’s disease, a disease that affects so many Americans.