Shark chemical wards off Parkinson's Disease

19 January 2017

A chemical found in sharks can block the process that leads to Parkinson's Disease, scientists at Cambridge University have found.

Know as squalamine, the substance prevents a protein called alpha-synuclein from accumulating on and damaging the membranes of nerve cells in the brain. Dosing with squalamine protected cells cultured in a dish as well as microscopic worms that have been genetically altered to make them develop a Parkinson's-like syndrome.

"Now we need to look into clinical trials to find out whether this will work in humans," says study lead author Chris Dobson.

Alpha-synuclein, which is a protein found normally in the brain, was first linked to Parkinson's Disease two decades ago. More recently scientists have discovered that, under certain circumstances it becomes misfolded and glues itself to the inside surfaces of the membranes that surround certain groups of nerve cells. This damages the membrane and stresses the cell, causing it to dysfunction and die.

Squalamine is a fatty molecule with a positive charge which is attracted to the negative charges present in the normal cell membrane. This enables it to get beneath the alpha-synuclein deposits as they try to form and prise them off the membrane, preventing them from doing harm to the cell.

Encouragingly, the team have also found evidence that squalamine can render harmless blobs of alpha-synuclein that have already aggregated. "So it might have both a therapeutic and preventative effect," points out Dobson, emphasising at the same time that no sharks were harmed in the study, which was published this week in PNAS.

"The amount of this molecule that is present in a dogfish shark is far too little to be useful. So we use a synthetic version."

Why the sharks make the molecule in the first place is a mystery though. "It does seem to have antibiotic properties," says Dobson. "In fact it's already been tested in humans for that and some other purposes, but never Parkinson's Disease."

The Cambridge team are working with collaborators in the US who are moving towards a clinical trial to study whether squalamine can impact on the rate at which Parkinson's progresses in patients.

"But we're also interested in looking at how this molecule works and then seeing if we can find a better one!"

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