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A cancer immunotherapy drug that is already on pharmacy shelves is showing fresh potential in the fight against Parkinson’s disease.

In mouse experiments, nivolumab–relatlimab, a fixed‑dose antibody combination used for treating melanoma, blocked the cell‑to‑cell spread of toxic protein clumps that drive the disorder.

More than 8.5 million people worldwide are living with Parkinson’s disease. Current drugs ease symptoms but do little to halt the relentless loss of movement, speech, and independence.

Xiaobo Mao of Johns Hopkins University led an international team that traced the blockade to a newly revealed partnership between two brain proteins, Aplp1 and LAG‑3. Their study offers a practical target for slowing disease progression.

How cancer drug blocks Parkinson’s

Alpha‑synuclein normally helps nerve cells chat across synapses, yet when it misfolds it becomes sticky and forms Lewy bodies.

The group discovered that Aplp1 and LAG‑3 act like twin door handles, swinging the misfolded cargo into neurons together.

“Now that we know how Aplp1 and LAG-3 interact, we have a new way of understanding how alpha‑synuclein contributes to the disease progression of Parkinson’s disease,” confirmed Mao.

Deleting either handle in genetically engineered mice cut protein uptake, but deleting both slashed it by 90 percent.

Using cultured neurons, the team showed that antibodies against LAG‑3 disrupted the partnership and kept most toxic fibrils outside. That hint of druggability set the stage for tests with the approved melanoma therapy.

Repurposing a cancer drug for Parkinson’s

Nivolumab–relatlimab, marketed as Opdualag^TM, won FDA clearance in 2022 as the first combination to target PD‑1 and LAG‑3 checkpoints in tumors.

Because relatlimab binds LAG‑3, the Parkinson’s team wondered whether it could also short‑circuit the neural handshake.

They injected the antibody mix into mice previously dosed with pathogenic fibrils. Treated animals accumulated far fewer Lewy‑like inclusions, keeping the midbrain’s dopamine supply and motor skills intact.

“The anti‑LAG-3 antibody was successful in preventing further spread of alpha‑synuclein seeds in the mouse models,” said Ted Dawson, also from Johns Hopkins.

The effect outperformed complete genetic knockout of LAG‑3 because the drug simultaneously disrupted its partner, Aplp1.

A protein traffic jam in the brain

The brain’s substantia nigra houses dopamine‑producing neurons that fine‑tune movement. When alpha‑synuclein fibrils march from cell to cell, these neurons choke and die, triggering tremor and rigidity.

LAG-3 had been flagged as a fibril receptor before, yet blocking it alone left plenty of pathology. The new work clarifies that Aplp1 forms a complex with LAG-3, which creates a high‑affinity docking site for toxic cargo.

By filming neurons with pH‑sensitive dye, researchers watched fibrils enter healthy cells in minutes. Removal of either handle delayed entry, while removal of both stopped it almost completely.

The discovery may explain why single‑target strategies have struggled to translate. Therapies that ignore Aplp1 risk leaving a back‑door route open for disease spread.

Why Parkinson’s is so difficult

Parkinson’s is diagnosed only after motor symptoms emerge, by which time over half of nigral dopamine neurons have perished. Lewy bodies start forming decades earlier and appear to propagate along neural highways.

Scientists debate whether the fibrils cause disease or merely mark dying cells, yet the correlation is strong enough that reducing their spread remains a key goal.

Animal studies that limit fibril movement often preserve motor behavior and cortical thinking.

The Aplp1–Lag3 duo offers a concise molecular explanation for long‑range propagation. It also supplies a measurable biomarker, their physical interaction, that drug developers can monitor.

Antibodies in action

Preclinical success seldom guarantees human benefit, yet repurposing an approved therapy skips many safety hurdles.

Opdualag’s^TM pharmacokinetics, dosing, and adverse‑event profile are already mapped in thousands of cancer patients.

The antibody crosses the mouse blood–brain barrier at roughly 0.5 percent of plasma levels, similar to other IgG medicines. That level sufficed to curb fibril uptake and protect motor performance in pole and cylinder tests.

If forthcoming primate and human studies confirm brain penetration, clinicians could move swiftly into small Parkinson’s trials using this cancer treatment drug. Outcome measures might track motor scores, cerebrospinal fibril counts, and imaging of nigral dopamine.

Parkinson’s gets help from cancer drug

Cancer checkpoint drugs can unleash immune‑related side effects, including rash, thyroid imbalance, and fatigue. Whether similar events would occur at lower neurological doses remains unknown.

Another question is timing. Most cancer antibodies are delivered in pulses, whereas chronic neuroprotection for Parkinson’s patients might require years of therapy.

Finally, fibril spread is only one facet of Parkinson’s biology. Mitochondrial stress, environmental toxins, and genetics also contribute, so a combination of treatments will likely be needed.

Even so, the ease of testing an off‑the‑shelf cancer medicine for Parkinson’s patients makes this avenue irresistible. As Dawson observed, stopping spread “could significantly slow the progression of Parkinson’s disease.”

The study is published in Nature Communications.

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A new study by investigators from Europe, including the Netherlands and the United Kingdom (UK), has shed light on significant ethical, administrative, regulatory, and logistical (EARL) hurdles in delivering multinational randomized clinical trials. The research was the first to comprehensively quantify these barriers for an international platform trial and emphasizes the need for urgent improvements, particularly in preparing for future public health crises.

Randomized controlled trials provide the highest level of evidence to inform medical practice. Yet, delivering such trials presents significant operational challenges and is becoming increasingly difficult. One of the many challenges of conducting high-quality, large-scale clinical research is ensuring compliance with all necessary ethical, administrative, regulatory, and logistical (EARL) requirements. In the event of severe infectious disease outbreaks requiring rapid action, EARL requirements and cross-country coordination make it challenging to implement clinical studies. The COVID-19 pandemic has demonstrated that there is wide variation in how countries approached clinical research in a public health emergency. However, the differences in timelines between countries have not been comprehensively quantified.

Comparing timelines

In this study, researchers quantified the timelines for EARL procedures, comparing different European countries. They used data from the Randomized Embedded Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP), which spanned both the pre-pandemic (2016-2020) and pandemic (2020-2023) periods. REMAP-CAP, an international clinical trial with an innovative adaptive platform design, was designed to test multiple drugs for the treatment of pneumonia, including COVID-19, which allowed for the comparison of a large number of submissions. The new analysis, published this week in JAMA Network Open, covered 257 fully signed contracts with study sites in 19 European countries and focused on three key metrics: time to complete site contracts, time to regulatory and ethical approval (TTA), and time to first patient enrollment (FPI).

Differences between countries

The results showed that the UK achieved dramatic gains in efficiency during the pandemic, with median contract completion time dropping by 97 percent: from 196 days pre-pandemic to just 5 days during the pandemic. In contrast, non-UK countries in Europe saw only an 18 percent decrease, with median times dropping from 224 to 183 days. The study also revealed stark differences in the time to ethical and regulatory approvals. Median TTA in the UK during the pandemic was 8 days, compared to 115 days in non-UK countries. Time from approval to first patient enrollment was, on average, three months faster in the UK (26 days versus 116 days).

These findings highlight the striking differences in research infrastructure and interpretation of regulatory guidelines across Europe. For researchers, it is clear that EARL processes in Europe can be a major bottleneck to trial initiation and execution, slowing down patient access to potentially life-saving therapies. But addressing these challenges requires proactive efforts, also from researchers themselves.”

Denise van Hout, MD, PhD (Research Program Epidemiology of Infectious Diseases, UMC Utrecht), epidemiologist, first author of the manuscript

Consistent, transparent processes

The researchers also noted that while the UK benefited from its established research networks and emergency trial frameworks, other countries continued to face considerable challenges. These differences underscore the need for harmonization of EARL procedures across countries to reduce delays and maximize the impact of collaborative trials.

“For researchers planning or conducting multinational studies, it is vital to acknowledge how preparation and engagement with ethical processes can contribute early on.” Van Hout emphasized. “Researchers, policymakers, legal experts, and regulators must collaborate to develop consistent, transparent processes that prioritize trial delivery without compromising safety and ethics. This also includes more efficient contracting. Greater collaboration and streamlining EARL procedures are essential to ensure that patients across Europe can benefit from innovative research, especially during future pandemics.”