Greek Myth Inspires Parkinson's Breakthrough

Credit: Scott Wiseman for The Wertheim UF Scripps Institute

Imagine a mythical beast with two heads, each playing a crucial role in vanquishing a foe. That's the image conjured by a promising new Parkinson's disease treatment emerging from the lab of chemist Matthew Disney, Ph.D.

The research is described in the Jan. 9 issue of the Proceedings of the National Academy of Sciences, or PNAS.

This "chimera" molecule, dubbed Syn-RiboTAC, boasts a dual-pronged attack on the disease: one head hunts down a key piece of Parkinson's-causing RNA, while the other goads the cell into chopping it up for recycling.

The research, published in the prestigious Proceedings of the National Academy of Sciences, offers a glimmer of hope for the millions battling Parkinson's. This debilitating disease robs people of brain cells and dopamine, causing tremors, rigidity, and a slew of other debilitating symptoms. Current treatments, while helpful, merely mask the disease and come with limitations.

"We need to strike at the root of Parkinson's: the toxic build-up of alpha-synuclein protein," explains Disney, chair of the chemistry department at Scripps Institute for Biomedical Innovation & Technology. But targeting this slippery, shapeless protein directly has proven tricky. That's where Syn-RiboTAC's chimeric nature comes in.

Instead of battling the protein itself, Syn-RiboTAC aims to nip the problem in the bud by targeting the RNA blueprint for alpha-synuclein. Think of it as cutting off the supply chain before the assembly line even starts. This novel approach, known as RNA knockdown, could revolutionize treatment for Parkinson's and other diseases with poorly druggable proteins.

Here's how it works: Disney's drug latches onto a specific section of the messenger RNA, the instruction manual for building proteins. Without this crucial "start" signal, the ribosomes, the cell's protein-making factories, are left idle. No alpha-synuclein? No Parkinson's symptoms.

Early tests in mouse models and human-derived neurons show promise. A mere 25% reduction in alpha-synuclein led to significant therapeutic benefits in mice, and human neurons treated with Syn-RiboTAC saw a 50% drop in the protein's production. Furthermore, the drug exhibited good selectivity, minimizing unwanted side effects, and displayed an impressive ability to cross the blood-brain barrier, reaching its target effectively.

While hurdles remain – refining the drug and navigating the lengthy journey to clinical trials – Disney and his team are optimistic. "The need for a game-changer in Parkinson's treatment is enormous," he says. "With Syn-RiboTAC, we believe we're paving the way for a brighter future for those living with this devastating disease."

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