AI Article Synopsis
- A study explored the potential therapeutic role of immune transformation for Parkinson's disease, building on over a decade of animal research showing that regulatory T cells (Tregs) could protect against neurodegeneration.
- A phase 1 trial involved 20 Parkinson's patients and 17 non-Parkinsonian controls to test the immune modulator sargramostim, revealing some modest improvements in symptoms and Treg function compared to the placebo group.
- While adverse events were reported in both groups (100% in sargramostim and 80% in placebo), the findings suggest that immune modulation may offer a new approach to treating Parkinson's disease, warranting further research with larger participant numbers.
Article Abstract
A potential therapeutic role for immune transformation in Parkinson's disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson's disease patients. Both Parkinson's disease patients and controls were monitored for 2 months for baseline profiling. Parkinson's disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson's disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson's disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson's disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445595 | PMC |
| http://dx.doi.org/10.1038/s41531-017-0013-5 | DOI Listing |
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