Researchers report that blocking the interaction between the host proteins LAG3 and APLP1 sharply reduces the spread of misfolded alpha-synuclein — the aggregates that drive Parkinson’s progression — in mouse models. Using the cancer immunotherapy combination nivolumab/relatlimab (which includes a LAG3-targeting antibody), double-knockout mice showed roughly a 90% drop in aggregate spread, and treated wild-type mice nearly halted propagation. These are early, mouse-only results; translating them to humans will require extensive safety and efficacy testing. The study highlights a promising drug-repurposing lead and complements other approaches such as advanced stem-cell and cellular-reprogramming research.
Existing Cancer Immunotherapy Dramatically Reduces Parkinson’s Protein Spread in Mice — A Promising Drug-Repurposing Lead
Researchers report that blocking the interaction between the host proteins LAG3 and APLP1 sharply reduces the spread of misfolded alpha-synuclein — the aggregates that drive Parkinson’s progression — in mouse models. Using the cancer immunotherapy combination nivolumab/relatlimab (which includes a LAG3-targeting antibody), double-knockout mice showed roughly a 90% drop in aggregate spread, and treated wild-type mice nearly halted propagation. These are early, mouse-only results; translating them to humans will require extensive safety and efficacy testing. The study highlights a promising drug-repurposing lead and complements other approaches such as advanced stem-cell and cellular-reprogramming research.
01:30, 04.11.2025Health
Existing cancer immunotherapy reduces spread of Parkinson’s protein in mice
Overview: Parkinson’s disease is progressive and currently incurable. Symptoms — including tremor, stiffness, balance and speech problems, and cognitive changes — worsen as dopamine-producing neurons in the substantia nigra are lost. A key driver of progression is the accumulation and cell-to-cell spread of misfolded alpha-synuclein aggregates (Lewy bodies), which displace normal cellular components and propagate pathology.
What researchers found: Earlier studies implicated two host proteins, LAG3 and APLP1, as partners that help toxic alpha-synuclein aggregates enter neurons. Removing LAG3 slowed spread but did not stop it, so investigators tested the combination of genetic deletion and pharmacologic blockade. They used the FDA-approved cancer immunotherapy combination nivolumab/relatlimab (relatlimab is an antibody that targets LAG3) to probe whether disrupting the LAG3–APLP1 interaction could reduce aggregate spread.
Key results (mouse models): In genetically modified mice lacking both LAG3 and APLP1 that received the drug, the team reported about a 90% reduction in the spread of harmful alpha-synuclein aggregates. In otherwise normal (wild-type) mice, treatment with nivolumab/relatlimab interfered with the LAG3–APLP1 interaction and nearly blocked propagation of disease-associated clumps.
Caveats and next steps: These results are preliminary and limited to animal models. Translating findings from mice to humans requires extensive additional research, including mechanistic studies, dose-finding, safety assessment and carefully designed clinical trials. Importantly, immune checkpoint therapies such as nivolumab/relatlimab have systemic immune effects and potential side effects that would need evaluation in the context of a chronic neurological disease.
Why this matters: The study highlights a potential drug-repurposing opportunity—using an existing, approved therapy to target a key pathway in Parkinson’s progression. It also adds to parallel approaches (advanced stem-cell strategies, cellular reprogramming, and therapies targeting harmful or senescent cells) aimed at slowing or reversing drivers of neurodegeneration.
Bottom line: The findings are encouraging but early. They point to a promising biological target (the LAG3–APLP1 interaction) and a possible repurposing pathway, while underscoring the need for much more research before any human application can be considered.