Foldable synthetic molecules could infiltrate and bust apart the toxic protein clumps causing Parkinson’s

Parkinson's disease and related conditions currently have therapies that only address symptoms, not the root cause: toxic clumps of proteins called alpha-synuclein. My research team created a synthetic molecule, SK-129, that can prevent these proteins from clumping and spreading in mice brains, reducing disease symptoms. SK-129 works by binding to different parts of alpha-synuclein, shaping it to be less likely to stick to other proteins.

This is part of a larger class of molecules called foldamers, which are laboratory-designed and can fold into predictable shapes. Foldamers' stability allows scientists to tailor them to target specific biological targets, a major advantage as many neurodegenerative disease proteins are considered "undruggable" due to their flexibility and lack of defined binding sites.

While SK-129 showed promise in cell and animal models, its effectiveness in humans hasn't been tested yet. Important questions remain about its long-term safety, optimal dosing, and how it interacts with the human body. Further studies are needed to understand the molecule's mechanisms and how to optimize it for treating Parkinson's in people.

Researchers are also investigating how selectively targeting these protein clumps affects their spread, inflammation, and brain cell survival across different regions. Other therapies targeting the same toxic alpha-synuclein clumps are also in development, including molecules to clear or reduce clumps and those that stop aggregation.

Each approach has limitations, but collaborative efforts between neuroscientists, biophysicists, and clinicians aim to develop new treatments for neurodegenerative diseases that conventional drugs have failed to address.