New Molecule Designed to Block the Protein Buildup Behind Parkinson's
🧠 What will you learn in this article?
This article highlights a new study that found a potential way to treat the underlying cause of Parkinson’s disease, not just its symptoms. It discusses how:
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In the brain, the abnormal clumping and spread of a protein called alpha-synuclein leads is tied to Parkinson’s. Current therapies address PD symptoms, not this process.
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Researchers developed SK-129, a molecule that can stop these clumps from forming and spreading in various models of Parkinson’s.
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In different models, SK-129 saved dopamine neurons and improved outcomes — protecting neurons even after damage began and boosting mouse survival while preventing movement impairment and brain inflammation.
In Parkinson’s disease (PD), a protein called alpha-synuclein misfolds and clumps together inside brain cells. These clumps are thought to damage neurons over time and can spread from cell to cell, driving the disease forward. Currently, treatments for PD only manage symptoms — none can slow or stop this underlying process.
Scientists are working hard to find disease-modifying therapies for Parkinson’s. A new study published in Science Translational Medicine may offer a path forward. Researchers at the University of Denver and NYU Abu Dhabi — co-led by Sunil Kumar, PhD, a Parkinson's Foundation Stanley Fahn Junior Faculty Awardee — have developed a special molecule called SK-129 that shows promise in blocking alpha-synuclein from clumping and spreading in the brain. The Parkinson’s Foundation directly funded this work.
Think of alpha-synuclein clumping like a chain reaction: one misfolded protein causes the next one to misfold, and so on, eventually building up harmful deposits. SK-129 is designed to interrupt that chain reaction before it gets started.
Because the SK-129 molecule interacts with important regions of alpha-synuclein, it can latch onto the misfolded protein and prevent it from recruiting others into clumps. Importantly, it targets the toxic, clumped forms of the protein rather than the healthy form, which has normal functions in the brain.
What is SK-129 and how does it impact Parkinson’s?
In Parkinson's, a protein called alpha-synuclein clumps inside brain cells.
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These clumps are thought to damage neurons and spread, making PD symptoms worse over time.
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Researchers developed a molecule called SK-129 that can stop these clumps from forming and spreading — stopping a chain reaction before it starts.
“Our study is unique in that it targets the most toxic forms of α-synuclein — oligomers — offering a new way to significantly slow disease symptoms. This approach creates hope for disease-modifying therapies not only for Parkinson’s, but also for related disorders like Lewy body dementia. That gives us real hope that disease-modifying therapies for Parkinson’s are within reach.”
- Dr. Kumar, study lead and Parkinson’s Foundation research grantee
Key advantages of SK-129 are its size and shape. Other strategies to block alpha-synuclein clumping, such as antibodies, are large molecules that struggle to cross the blood-brain barrier (the protective layer between the bloodstream and the brain). SK-129 is small and compact enough to cross this barrier. Additionally, once in the brain, the molecule was able to stay there for multiple days, which is essential for sustained treatment.
Study Results
The research team tested SK-129 across a remarkably wide range of models — from human cells and patient-derived tissue to worm and mouse models of PD.
In worm models of PD, untreated worms lost most of their dopamine-producing neurons over time. Worms treated preventatively with SK-129 retained nearly all of them, along with restored movement and behavior. Critically, SK-129 may be more than a preventive measure. When given after disease had already set in — after about 30% of dopamine neurons had already been lost — it still rescued a significant number of remaining neurons. This is important because people with Parkinson’s are typically diagnosed after symptoms have already appeared.
In a mouse model of PD, untreated mice survived an average of about 175 days, with fewer than 20% surviving to 270 days. Those that survived showed severe movement problems. In contrast, mice treated with SK-129 had 100% survival to 270 days and showed no signs of movement impairment. Brain tissue from treated mice showed no harmful protein deposits or signs of brain inflammation.
To test the molecule in human samples, the researchers tested SK-129 using exosomes — tiny cellular packages — isolated from the blood of people with Parkinson’s. These exosomes carried misfolded alpha-synuclein that could trigger clumping in cells grown in a petri dish. Adding SK-129 blocked this process.
Another interesting finding was that SK-129 also blocked alpha-synuclein from clumping together with tau, a protein linked to Alzheimer’s disease. Tau is increasingly recognized as being important in Parkinson’s too; about half of people with PD also have tau-related brain changes, which can worsen both movement and cognitive symptoms. In the mouse model, treated mice showed no evidence of combined alpha-synuclein and tau deposits, while untreated mice did. In short, while SK-129 is designed to target harmful alpha-synuclein deposits, it also prevented alpha-synuclein from clumping with tau as well.
Highlights
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Researchers developed a molecule, called SK-129, that can make it to the brain and attach to toxic forms of the protein associated with Parkinson’s called alpha-synuclein.
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SK-129 latches onto the hallmark PD protein and prevents it from launching a clumping chain reaction.
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In multiple models of PD (including cells, worms, mice and human-derived tissue), treatment with SK-129 prevented alpha-synuclein clumping and rescued signs of neurodegeneration.
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SK-129 shows promising therapeutic properties, including the ability to effectively reach the brain, preferentially bind to toxic forms of alpha-synuclein, and remain in brain tissue for a prolonged period of time.
What Does This Mean?
While early, SK-129 has the potential to be a breakthrough Parkinson’s treatment. This study represents an important step toward a long-sought goal: a disease-modifying treatment that addresses the underlying cause of Parkinson’s disease instead of only symptoms.
This research supports a promising strategy at the forefront of Parkinson’s research: targeting the clumping and spread of alpha-synuclein, a suspected driver of PD progression. Earlier approaches have struggled because they were not specific enough, couldn’t enter the brain or didn’t last long enough in the brain to be effective.
Importantly, SK-129’s unique features have overcome many of these challenges, making it a promising potential therapy. Despite this progress, SK-129 still needs thorough safety testing and studies in more complex models before clinical trials can begin, so it will likely be years before it is available. This is why funding a diverse range of Parkinson’s research studies is so important.
What Do These Findings Mean for People with Parkinson’s Right Now?
SK-129 is not yet a treatment available to people. It is still in the preclinical stage, with next steps already underway.
“Next, we’ll move SK-129 toward clinical development by testing its safety and dosing,” said Dr. Kumar. “A key priority is to establish a clear link between dose, effectively targeting the harmful alpha-synuclein and producing real benefits in animal models. At the same time, we are optimizing related molecules to improve strength, access to the brain and stability, to help identify the best candidate for future clinical trials.”
For people with Parkinson’s, continue current care — medications, exercise, therapy) — and consider clinical trials if interested. While SK-129 is likely years away from human testing, the development of molecules like this represents meaningful progress and demonstrates the importance of supporting preclinical Parkinson’s research.
Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD treatments and ongoing research through our resources below, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.
