FDA-Approved Cancer Drug Shown to Halt Parkinson’s Disease

What if the answer to slowing one of the most relentless brain diseases wasn’t in a new invention but in a cancer drug already sitting on pharmacy shelves?

Parkinson’s disease affects more than 8.5 million people worldwide. It creeps in gradually one tremor, one shuffle, one lost expression at a time silently dismantling the brain’s control over movement, mood, and memory. For decades, treatment has focused on easing symptoms, but the disease has always marched forward.

Now, a breakthrough from neuroscientists at Johns Hopkins is changing that narrative. Their research has uncovered a surprising biological partnership two proteins working together to help Parkinson’s spread through the brain. Even more surprising? An FDA-approved cancer drug appears to break up that partnership and stop the damage before it takes hold.

This could be a turning point not just for Parkinson’s, but for how we approach diseases driven by toxic protein buildup.

How Parkinson’s Disease Really Spreads

Parkinson’s disease isn’t just about low dopamine it’s a disorder fueled by toxic protein spread. The main culprit is a protein called alpha-synuclein, which normally helps neurons communicate. But when it misfolds, it becomes harmful. These misfolded alpha-synuclein proteins clump together, forming what are known as Lewy bodies. They don’t stay put. They move from one neuron to another, triggering a chain reaction that turns healthy proteins into toxic ones.

This process mirrors how prions spread in diseases like Creutzfeldt-Jakob. Once inside a cell, misfolded alpha-synuclein causes dysfunction, inflammation, and eventually a specific kind of programmed cell death. Over time, this cascade leads to the loss of dopamine-producing neurons in a part of the brain called the substantia nigra the core reason for the tremors, stiffness, and slowed movement that define Parkinson’s.

Importantly, this spread isn’t random. The toxic proteins rely on specific entry points on the surface of neurons—proteins that act like doorways. Until recently, researchers only had a partial picture of how alpha-synuclein gained access. That changed when two key proteins, Aplp1 and Lag3, were identified as major enablers. These proteins don’t just allow entry they accelerate it, making the disease spread faster and more aggressively.

How Parkinson’s Disease Really Spreads

Parkinson’s disease isn’t just about low dopamine it’s a disorder fueled by toxic protein spread. The main culprit is a protein called alpha-synuclein, which normally helps neurons communicate. But when it misfolds, it becomes harmful. These misfolded alpha-synuclein proteins clump together, forming what are known as Lewy bodies. They don’t stay put. They move from one neuron to another, triggering a chain reaction that turns healthy proteins into toxic ones.

This process mirrors how prions spread in diseases like Creutzfeldt-Jakob. Once inside a cell, misfolded alpha-synuclein causes dysfunction, inflammation, and eventually a specific kind of programmed cell death. Over time, this cascade leads to the loss of dopamine-producing neurons in a part of the brain called the substantia nigra the core reason for the tremors, stiffness, and slowed movement that define Parkinson’s.

Importantly, this spread isn’t random. The toxic proteins rely on specific entry points on the surface of neurons—proteins that act like doorways. Until recently, researchers only had a partial picture of how alpha-synuclein gained access. That changed when two key proteins, Aplp1 and Lag3, were identified as major enablers. These proteins don’t just allow entry they accelerate it, making the disease spread faster and more aggressively.

Two Proteins at the Heart of the Problem

Aplp1: the unexpected accomplice
Aplp1 is a single-pass membrane protein best known for helping synapses hold their shape. Johns Hopkins investigators found that its large “E1” domain grabs misfolded alpha-synuclein fibrils with nanomolar affinity, but ignores the harmless monomeric form. When neurons lack Aplp1, internalization of these toxic fibrils drops by roughly 40 percent, and the usual buildup of Lewy-body pathology slows.

Lag3: an immune checkpoint with a neuronal side job
Lag3 is already familiar to oncologists because drugs that block it (relatlimab, for example) boost immune attack against tumors. Neurologists are now paying attention too. Lag3 sits on the surface of about half of cortical neurons and, like Aplp1, binds alpha-synuclein fibrils. Deleting Lag3 alone produces only partial protection, suggesting another partner is involved.

“Our work previously demonstrated that Lag3 wasn’t the only cell-surface protein that helped neurons absorb alpha-synuclein, so we turned to Aplp1 in our most recent experiments,” explains neuroscientist Valina Dawson, PhD.

Synergy that accelerates disease
Aplp1 and Lag3 share a seven-amino-acid motif (GG/LRSGR) that acts like a common docking clamp for alpha-synuclein. When both proteins are present, the amount of toxic fibril pulled into neurons is greater than the sum of their individual contributions an effect confirmed in double-knockout mice, where uptake and spread fell by more than 90 percent. Those mice kept their dopamine neurons and showed no Parkinson-like motor deficits on pole and cylinder tests.

Why this pairing matters
The Aplp1-Lag3 complex doesn’t just bind alpha-synuclein; it actively draws the fibrils deep into the cell via endocytosis. Break that complex and the chain reaction that drives Parkinson’s grinds to a halt. In fact, an anti-Lag3 antibody already approved for melanoma severed this partnership and outperformed genetic deletion in protecting mouse brains.

“The anti-Lag3 antibody prevented further spread of alpha-synuclein seeds and did better than Lag3 knockout because of Aplp1’s tight association,” notes Ted Dawson, MD, PhD.

These findings position Aplp1 and Lag3 not dopamine alone as prime therapeutic targets. Blocking their combined “doorway” could, for the first time, shut down the engine that drives Parkinson’s progression.

How a Cancer Drug Blocks Parkinson’s Progression

The most promising intervention in this research didn’t come from a newly engineered molecule it came from a cancer drug already in clinical use. The antibody, known as relatlimab, was originally developed to block Lag3, a protein that acts as an immune checkpoint in cancer. But in the brain, this same protein enables the spread of toxic alpha-synuclein.

Researchers at Johns Hopkins repurposed relatlimab to see if it could disrupt the Aplp1-Lag3 interaction that accelerates Parkinson’s progression. It worked. When administered to mice with Parkinson’s-like pathology, the antibody halted the spread of alpha-synuclein fibrils, preserved dopamine-producing neurons, and eliminated motor symptoms typically caused by the disease. In key brain regions like the substantia nigra and cortex signs of disease were sharply reduced.

One of the most significant findings: the antibody outperformed genetic deletion of Lag3. While deleting Lag3 alone reduced alpha-synuclein uptake, the antibody did more because it also blocked the Lag3-Aplp1 complex, the true driver of cellular uptake and toxicity. In other words, the antibody didn’t just remove one component—it disrupted the partnership that made disease progression possible.

Just as important, the drug crossed the blood-brain barrier, a major hurdle for most neurological therapies. Low but effective concentrations were detected in cerebrospinal fluid within days after a single dose, and its effects persisted with weekly treatments over several months.

This opens the door to a fast-track path for clinical trials. Because relatlimab is already FDA-approved for melanoma, its safety profile in humans is well-documented. The possibility of redirecting an existing drug to target the mechanism behind Parkinson’s not just the symptoms represents a major shift in how we approach treatment. For the first time, science is not just managing the disease, but interfering with its engine.

What This Means for Treatment—Realistic Possibilities and Limitations

The discovery that a cancer drug can block the spread of alpha-synuclein marks a major step forward but it’s not a cure, and it’s not ready for clinics yet. What this research offers is a clear, actionable strategy for slowing or even halting Parkinson’s progression by targeting the disease at its source: the cell-to-cell transmission of toxic protein.

Unlike current treatments, which focus on replacing dopamine or managing symptoms, this approach addresses the underlying pathology. By blocking the Aplp1-Lag3 interaction, the drug prevents alpha-synuclein from entering neurons and triggering the cascade of degeneration. In preclinical models, this led to significant preservation of brain tissue and complete prevention of motor deficits.

Importantly, the therapy showed greater effectiveness than deleting Lag3 or Aplp1 alone, confirming that both proteins contribute independently and synergistically to disease spread. The use of an FDA-approved antibody (relatlimab) also shortens the development timeline for clinical trials. This avoids the years typically required to prove basic safety.

That said, mouse models do not fully reflect human neurobiology. Clinical trials will need to confirm whether blocking Aplp1-Lag3 slows progression in people already diagnosed, or if it’s more effective as a preventive therapy in early-stage disease. Long-term safety, dosage, and potential immune side effects also need to be carefully evaluated, especially since Lag3 plays a role in immune regulation.

The data so far are compelling: in mice, blocking this pathway preserved dopamine levels, reduced brain pathology, and protected motor function. But moving from lab bench to bedside will require more than promising results—it will require well-designed human trials, careful patient selection, and monitoring for both neurological and immunological effects.

What This Means for Patients and Caregivers

If you or someone you care about is living with Parkinson’s, this research offers a reason to pay attention but not to panic, overhype, or expect immediate changes in clinical care. Here’s what matters most right now:

1. This is not a treatment you can ask for yet.
The cancer drug used in the study, relatlimab, is FDA-approved for melanoma but not for Parkinson’s. While its ability to block the Aplp1-Lag3 interaction is promising, it has not yet been tested in human patients with neurodegenerative disease. Clinical trials will be necessary before it’s considered a treatment option.

2. It targets progression not just symptoms.
Current Parkinson’s medications improve daily function but don’t stop the disease from advancing. This new approach is focused on halting the spread of the disease-causing protein alpha-synuclein. That distinction matters: it means this research could shift the treatment model from symptom control to disease modification.

3. Early diagnosis still matters.
If future therapies can block disease progression, catching Parkinson’s early before major neuron loss will be key. If you notice early warning signs like tremors, changes in handwriting, or subtle movement issues, don’t delay seeking medical advice.

4. Stay informed about clinical trials.
Trials testing this approach in humans may be on the horizon. Organizations like Fox Trial Finder, ClinicalTrials.gov, and the Michael J. Fox Foundation regularly post trial opportunities. Patients and families who stay engaged and informed will have the clearest path to participate when studies open.

5. Keep managing what you can today.
This research is encouraging, but it doesn’t replace existing treatments. Regular follow-ups with a neurologist, a balanced medication plan, exercise, sleep hygiene, and support networks are still essential. Lifestyle habits still play a meaningful role in quality of life.

Reframing the Fight Against Parkinson’s

For decades, Parkinson’s disease has followed a frustrating pattern: slow onset, steady progression, and no way to stop it. Treatments have helped manage symptoms, but the disease always found a way forward. This new research shifts the equation. By identifying how alpha-synuclein spreads and showing that an existing cancer drug can block the process, scientists have opened the door to a true disease-modifying therapy.

Disrupting the Aplp1-Lag3 interaction not only slowed disease progression in lab models it protected brain cells, preserved movement, and reduced pathology to levels not seen with standard interventions. More importantly, it points to a real-world, actionable path using a drug that’s already available.

Still, human trials are essential. There’s no shortcut around the need for long-term safety and effectiveness data in actual Parkinson’s patients. But for the first time, researchers aren’t just talking about slowing the symptoms they’re working to stop the disease from spreading at all.

The message for patients, caregivers, and clinicians is clear: the research landscape for Parkinson’s is changing. Staying engaged, informed, and involved is now more valuable than ever.

Sources:

1. Sordo-Bahamonde, C., Lorenzo-Herrero, S., González-Rodríguez, A. P., Payer, Á. R., González-García, E., López-Soto, A., & Gonzalez, S. (2021). LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia. Cancers, 13(9), 2112. https://doi.org/10.3390/cancers13092112
2. Mao, X., Gu, H., Kim, D., Kimura, Y., Wang, N., Xu, E., Kumbhar, R., Ming, X., Wang, H., Chen, C., Zhang, S., Jia, C., Liu, Y., Bian, H., Karuppagounder, S. S., Akkentli, F., Chen, Q., Jia, L., Hwang, H., . . . Dawson, T. M. (2024). Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-49016-3