Table 3 Drugs against neuroinflammation currently tested in clinical trial found on ClinicalTrials.gov [103] and the ISRCTN registry
From: Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases
Name/phase | Features | Identifier | Duration |
|---|---|---|---|
General immune response | |||
Trehalose (SLS-005)/phase II | Disaccharide able to promote autophagy and the immune response [117] | NCT05332678 | 2023 2025 |
Senicapoc/phase II | Calcium-activated potassium channel KCa3.1 inhibitor to reduce neuroinflammation [118] | NCT04804241 | 2022 2025 |
Baricitinib/phase I and II | Janus kinase inhibitor able to reduce neuroinflammation [119] | NCT05189106 | 2022 2024 |
CpG1018/phase I | Synthetic oligodeoxynucleotides that mimic bacterial DNA and trigger the immune system with unmethylated CpG dinucleotides located in CpG motifs [120] | NCT05606341 | 2023 2024 |
Microglial target | |||
Oligomannate (GV-971)/phase IV | Marine-derived oligosaccharide. In the gut it reconstitutes microbiota, reduce peripheral immune cells infiltration into the brain, inhibiting neuroinflammation. In the brain it prevents Aβ formation and deposition [121] | NCT05058040 NCT05181475 | 2021 2025 |
Sargramostim/phase II | Pro-inflammatory cytokine granulocyte–macrophage colony-stimulating factor, transforming microglia, reducing amyloid load, increasing synaptic area, and improving memory [122] | NCT04902703 | 2022 2024 |
AL002/phase II | Humanized IgG1 that binds to and inactivate the TREM2 [123] | NCT05744401 | 2023 2025 |
Daratumumab/phase II | Human monoclonal antibody that binds to CD38, marker of senescent microglia [119] | NCT04070378 | 2019 2024 |
Specific immune response | |||
Canakinumab/phase II | Monoclonal antibody against Interleukin-1β to reduce neuroinflammation [124] | NCT04795466 | 2021 2026 |
Lenalidomide/phase II | Immunomodulator increasing anti-inflammatory cytokines levels and decreasing TNF-α, IL-6, IL-8 levels | NCT04032626 | 2022 2024 |
XPro1595/phase II | PEGylated human TNF emulator lacking TNF receptor-binding activity that binds and sequesters native TNF [125] | NCT05522387 NCT05318976 | 2022 2025 |
Masitinib/phase III | Tyrosine kinase inhibitor that can accumulate in the CNS and inhibit mast cells and microglia/macrophages | NCT05564169 | 2022 2025 |
Azathioprine/phase II | Purine antagonist limiting the proliferation of lymphocytes [126] | ISRCTN14616801 | 2018 2024 |
Sargramostim/phase I | T-lymphocyte populations regulator by boosting the T-regulatory cells and suppressing T-effector function, to reduce the chronic activation | NCT05677633 | 2023 2024 |