Table 1.
Preclinical animal and laboratory studies.
| Route of delivery | CMT | Delivery | Target | Stage | Mechanism result |
|---|---|---|---|---|---|
| Intrathecal Intravenous | CMT2A | AAV8 | SARM1 | In vivo | Reduced axonal degeneration (11) |
| CMT2D | AAV9 | GARS | In vivo | Delayed axonal degeneration (12) | |
| CMT2E | CRISPR/Cas9 | NEFL | In vivo | Phenotypic rescue (13) | |
| CMT2S | AAV9 | IGHMBP2 | Phase 1 clinical trial | Phenotypic rescue (14) | |
| Intrathecal Intra-nerve Intravenous | CMT1X | AAV9 | MPZ, GJB1 | In vivo | Phenotypic rescue (15) |
| LV | MPZ, GJB1 | In vivo | Phenotypic improvement (16) | ||
| CMT4C | LV | SH3TC2 | In vivo | Incomplete rescue (17) | |
| CMT4J | AAV9 | CBA, FIG4 | In vivo | Incomplete rescue (18) | |
| CMT1B | LV | MANF | In vivo | Protective effect (19) | |
| CMT1A | AAV9 | PMP22, shRNA | In vivo | Improved myelination (20) | |
| PMP22, miR | In vivo | Phenotypic rescue (21) | |||
| LV | PMP22, shRNA | In vivo | Rescue of myelination (22) | ||
| Squalene NP | PMP22, siRNA | In vivo | Functional recovery (23) | ||
| CRISPR/Cas9 | PMP22 | In vivo | Myelination rescue (24) | ||
| ASO | PMP22 | In vivo | Phenotypic improvement (25) | ||
| Intra-muscular | CMT1A | AAV1 | NT-3 | Phase 1 clinical trial | Histologic functional improvement (26) |
| CMT1X | AAV1 | NT-3 | In vivo | Phenotypic improvement (27) | |
| CMT2D | AAV1 | NT-3 | In vivo | Phenotypic improvement (28) |
AAV, adeno-associated virus; LV, lentivirus; NP, nanoparticles; SARM1, sterile alpha and TIR motif containing 1; miR, microRNA; IGHMBP2, immunoglobulin mu DNA binding protein 2; MPZ, myelin protein zero; GJB1, gap junction beta 1; SH3TC2, SH3 domain and tetratricopeptide repeats 2; CBA, chicken β-actin; MANF, Mesencephalic astrocyte-derived neurotrophic factor; shRNA, small hairpin RNA; siRNA, short interfering RNA; NT-3, neurotrophin-3; HPHGF, human paracrine hepatocyte growth factor.