{"doi":"10.1016/j.ebiom.2021.103380","title":"Safety, tolerability, and immune-biomarker profiling for year-long sargramostim treatment of Parkinson's disease","abstract":"BACKGROUND: Neuroinflammation plays a pathogenic role in Parkinson's disease (PD). Immunotherapies that restore brain homeostasis can mitigate neurodegeneration by transforming T cell phenotypes. Sargramostim has gained considerable attention as an immune transformer through laboratory bench to bedside clinical studies. However, its therapeutic use has been offset by dose-dependent adverse events. Therefore, we performed a reduced drug dose regimen to evaluate safety and to uncover novel disease-linked biomarkers during 5 days/week sargramostim treatments for one year. METHODS: Five PD subjects were enrolled in a Phase 1b, unblinded, open-label study to assess safety and tolerability of 3 μg/kg/day sargramostim. Complete blood counts and chemistry profiles, physical examinations, adverse events (AEs), immune profiling, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, T cell phenotypes/function, DNA methylation, and gene and protein patterns were evaluated. FINDINGS: Sargramostim administered at 3 μg/kg/day significantly reduced numbers and severity of AEs/subject/month compared to 6 μg/kg/day treatment. While MDS-UPDRS Part III score reductions were recorded, peripheral blood immunoregulatory phenotypes and function were elevated. Hypomethylation of upstream FOXP3 DNA elements was also increased. INTERPRETATION: Long-term sargramostim treatment at 3 μg/kg/day is well-tolerated and effective in restoring immune homeostasis. There were decreased numbers and severity of AEs and restored peripheral immune function coordinate with increased numbers and function of Treg. MDS-UPDRS Part III scores did not worsen. Larger patient numbers need be evaluated to assess conclusive drug efficacy (ClinicalTrials.gov NCT03790670). FUNDING: The research was supported by community funds to the University of Nebraska Foundation and federal research support from 5 R01NS034239-25.","journal":"EBioMedicine","year":2021,"id":155525,"datarank":1.1556687716371128,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":0.5440381550512546,"self_endowment_contribution":0.611630616585858,"citer_contribution":0.5440381550512546,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":36,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03790670"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":470671,"name":"Krista L. Namminga","orcid":null,"position":1,"is_corresponding":false},{"id":470672,"name":"Yaman Lu","orcid":null,"position":2,"is_corresponding":false},{"id":469942,"name":"Aaron Schwab","orcid":"0000-0003-1142-7790","position":3,"is_corresponding":false},{"id":469943,"name":"Mackenzie J. Thurston","orcid":"0000-0001-7622-3305","position":4,"is_corresponding":false},{"id":627856,"name":"Mai Mohamed Abdelmoaty","orcid":"0000-0001-7672-7052","position":5,"is_corresponding":false},{"id":320558,"name":"Vikas Kumar","orcid":"0000-0001-7513-6832","position":6,"is_corresponding":false},{"id":658284,"name":"Melinda Wojtkiewicz","orcid":"0000-0001-8029-4536","position":7,"is_corresponding":false},{"id":659173,"name":"Helen Obaro","orcid":null,"position":8,"is_corresponding":false},{"id":658285,"name":"Pamela M. Santamaria","orcid":"0000-0002-5892-4631","position":9,"is_corresponding":false},{"id":266818,"name":"R. Lee Mosley","orcid":"0000-0002-4241-6149","position":10,"is_corresponding":false},{"id":109790,"name":"Howard E. Gendelman","orcid":"0000-0002-7831-0370","position":11,"is_corresponding":false},{"id":266817,"name":"Katherine E. Olson","orcid":"0000-0003-2565-2438","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:44:03.750995Z","pmid":"34000620","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}