Table 3.
Neuroprotective and regenerative effects of small-molecule enzyme substrates and inhibitors reported in two or more separate articles.
| Outcome | 4-Aminopyridine* | BLZ945 | Ellagic acid | Metformin* | Miconazole* | Nimodipine | Pregabalin* |
|---|---|---|---|---|---|---|---|
| Increased viability of OPC and/or OLG | ✓ | ✓ | ✓ | ✓ | ✓ | ||
| Preserved quantity, function, or integrity of neurons/axons | ✓ | ✓ | ✓ | ✓ | |||
| Protected against myelin loss and/or atrophy and lesions | ✓✓ | ✓ | ✓ | ✓✓ | ✓✓ | ✓✓ | |
| Reduced CNS oxidative stress, apoptosis, or cellular dysfunction | ✓ | ✓ | ✓ | ||||
| Suppressed inflammatory microglial and/or astrocyte activation | ✓✓ | ✓ | ✓ | ✓ | ✓ | ||
| Promoted NPC/OPC proliferation or differentiation | ✓✓ | ✓ | ✓ | ||||
| Induced formation of new myelin | ✓✓ | ✓✓ | ✓ | ✓ | |||
| Increased clearance of axonal myelin debris | ✓ | ||||||
| Suppressed myelin inhibitory factors | ✓ | ||||||
| Improved neurological function (physical or cognitive) | ✓✓ | ✓ | ✓ | ✓ | ✓✓ | ✓✓ | |
| Relevant miscellaneous effect | Changes in DTI measures in treated PwMS | Increased sphingolipid levels in spinal cord | |||||
| Animal models/clinical studies | Human observational, pilot, and phase IV trial | Cuprizone and EAE | Cuprizone and EAE | Cuprizone and EtBr | LPC, EAE, and NMO | EAE | LPC and EAE |
DTI: diffusion tensor imaging; EAE: experimental autoimmune encephalomyelitis; EtBr: ethidium bromide; LPC: lysophosphatidylcholine; NMO: neuromyelitis optica; NPC: neural precursor cell; OLG: oligodendrocyte; OPC: oligodendrocyte precursor cell; PwMS: persons with multiple sclerosis.
Each check (✓) represents an observed outcome from an individual study.
*
Indicates existing FDA or Health Canada approval.