Active and passive immunization studies in PD animal models
| Type | Name | Antibody | Model | Route | Time and dose | Target site | Effect on α-Syn | Effect on behavior | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Active | PDO1A AFFiRiS | AFF | PDGF, mThy1, MBP α-Syn mice | s.c. | 8 months; 80 μg/mL, 100 μL | C-terminus | ↓ α-Syn accumulation prevented α-Syn spreading | Motor improvements: ↓ errors on round beam test | [44, 45] |
| PDO3A AFFiRiS | PLP α-Syn mice | Preserved nigral DA neurons ↓ α-Syn olig levels and microglial activation | Improved gait deficits Motor improvements: ↓ errors on round beam test | [46] | |||||
| UB-312 Vaxxinity | UB-312 | Thy1SNCA/15 mice (line 61) | i.m. | 15 months; 40 µg per injection | C-terminus | ↓ Levels of α-Syn olig | Motor, learning, and memory improvements: ↓ errors on round beam ↓ Path and latency to platform in water maze and challenging beam test | [47–51] | |
| Passive | Prasinezumab (PRX002) | 9E4 | PDGF, Thy1 (line D, 61)-α-Syn mice | i.p./i.v. | 6 months; 10 mg/kg | C-terminus | ↓ DA cell loss ↓ Calpain-cleaved α-Syn olig ↓ α-Syn accumulation | Motor performance: ↑ Cylinder, Pole, and Rotarod test | [45, 51, 52] |
| Cinpanemab | BIIB054 (NI-202) | Rat and cynomolgus monkey. A53T (M83), BAC A53T α-Syn PFF | i.p./i.v. | 2–4 months; 10 mg/kg and 30 mg/kg | N-terminus | ↓ α-Syn pathology preserved and improved DAT levels | Motor improvements: ↑ latency in time to fall in wire hang test | [53, 54] | |
| TAK-341 | MEDI1341 | Rat and cynomolgus monkey | i.v. | 13 weeks; from 3 mg/kg to 100 mg/kg; 25, 75, and 150 mg/kg | C-terminus | ↓ Contralateral and ipsilateral α-Syn ↓ Interstitial and CSF fluid α-Syn levels ↓ α-Syn propagation along axons | - | [55] | |
| ABBV-0805, BAN0805 | ABBV-0805, mAb47 | A53T, Thy1-A30P | i.p./i.v. | 2–4 months; 0.1, 1, 10, and 20 mg/kg | C-terminus; protofibrils | ↓ Soluble and insoluble α-Syn ↓ pS129 α-Syn pathology | ↑ Mean survival on A30P mice | [56–58] | |
| Lu AF82422 | Rat and cynomolgus monkey | i.v. | 4 weeks, 1 dose; 0–600, 0–300, and 1–30 mg/kg | C-terminus | ↓ α-Syn in plasma and CSF | - | - | [59] | |
| Ab274 | PDGFb (line M) α-Syn mice | i.p. | 4 weeks; 1 mg/mL | C-terminus | ↓ NeuN cell loss; ↑ Cathepsin-D and α-Syn; ↑ α-Syn clearance by microglial; ↓ TNF-α and IL-6; ↑ Iba-1; ↓ α-Syn (70–80%) | ↓ Latency to turn (Pole test) ↓ Total activity in the open field and Pole test | ↓ Latency to turn (Pole test) ↓ Total activity in the open field and Pole test | [47] | |
| 1H7, 5C1 | Thy1 α-Syn (line 61) mice | i.p. | 6 months; 10 mg/kg | C-terminus | ↓ TH loss in striatum (35%) ↓ α-Syn aggregation ↑ Synaptophysin + MAP2 ↓ Astro and microgliosis | ↓ Memory and learning deficits ↓ Error on transversal beam ↓ Memory and learning deficits | ↓ Memory and learning deficits ↓ Error on transversal beam ↓ Memory and learning deficits | [45] | |
| AB1 | Nigral AAV-CBA α-Syn in wt rats | i.p. | 3 months; 1 mg/rat (2x first), 0.5 mg/mL | N-terminus | ↓ α-Syn in SN ↓ α-Syn brain homogenate ↓ DA and NeuN cells loss | Motor improvement: ↑ on Cylinder test | Motor improvement: ↑ on Cylinder test | [60] | |
| AB2 | C-terminus | ||||||||
| Syn303 | wt mice PFF | i.p. | 180 days; 30 mg/kg | N-terminus | Blocked α-Syn spreading ↓ DA cells loss ↓ Insoluble α-Syn aggregation and pS129-α-Syn | ↑ Latency to hang (wire-hang time) | ↑ Latency to hang (wire-hang time) | [61] | |
| Syn-O1 | mThy1 (line 61) α-Syn mice | i.p | 3 months; 30 mg/kg | Oligos | ↓ α-Syn accumulation | - | - | - | |
| Syn-O4 | Oligos | ↓ NeuN cell loss | - | - | - | ||||
| Syn-F1 | Fibrils | ↓ Oligomeric α-Syn | - | - | - |
↓: decreased; ↑: increased; -: not applicable. MBP: myelin basic protein; NeuN: neuronal nuclei; MAP2: microtubule-associated protein 2; Iba-1: ionized calcium-binding adapter molecule 1
