Table 1.
Different routes of NTFs delivery and therapies in pre-clinical models.
| NTF | Delivery route | Model | Outcomes | References |
|---|---|---|---|---|
| RECOMBINANT NEUROTROPHIC GROWTH FACTORS | ||||
| CNTF | I.P | pmn/pmn mice (20–21 d) | MP+, S+ | (11) |
| S.C | Wobbler mice | MP+, MC+ | (12–14) | |
| BDNF | S.C | Wobbler mice | MP+ | (14) |
| GDNF | S.C | pmn/pmn mice (15–18 d) | No effect | (15) |
| VEGF | I.P | SOD1G93A mice (74 d) | MP+, DDO+, S+11 d | (16) |
| I.C.V | SOD1G93A/LSd rats (60 d) | MP+, DDO+, S+10 d | (17) | |
| I.S.P | Excitotoxic model in rats | MP+, DDO+, S+10.5 d, +5 d | (18, 19) | |
| Viral vector based gene therapy | ||||
| AAV-NTF | ||||
| IGF-1 | I.M | SOD1G93A mice (90 d) | MP+, S+22 d | (20) |
| I.S.P | SOD1G93A mice (60 d) | MP+, DDO+, S+12.3 d ♂ | (21) | |
| In D.C.N | SOD1G93A mice (88–90 d) | MP+, S+14 d | (22) | |
| I.M | SOD1G93A mice (60 and 90 d) | MP+, DDO+, S+29 d and +15 d ♂, +24 d and +14 d ♀ | (23) | |
| I.V | SOD1G93A mice (90 d) | MP+, S+10 d | (24) | |
| I.C.V | SOD1G93A mice (80–90 d) | DDO+, S+12 d | (25) | |
| VEGF | I.C.V | SOD1G93A mice (80–90 d) | DDO+, S+9 d ♂, +20 d ♀ | (25) |
| I.T | SOD1G93A mice (90 d) | DDO+, S+12 d | (26) | |
| GDNF | I.M | SOD1G93A mice (90 d) | MP+, DDO+, S+16.6 d | (27) |
| I.V | SOD1G93A rats (25 d) | MP +/–, S– | (28) | |
| G-CSF | I.S.P | SOD1G93A mice (70 d) | MP+, DDO+, S+ | (29) |
| Stem cell based therapy | ||||
| AAV-NTF | ||||
| hSC-NSC | I.S.P | SOD1G93A rats (56–62 d) | MP+, DDO+, S+11 d | (30, 31) |
| gm hNSC line (VEGF) | I.T | SOD1G93A mice (70 d) | DDO+, S+12 d | (32) |
| hSC-NPC | I.S.P | SOD1G93A mice (40 d) | MP+, S+5 d | (33) |
| gm hNPC (GDNF) | I.S.P | SOD1G93A rats (~80 d) rats (~80 d) | MP–, S– | (34, 35) |
| Cortex | SOD1G93A rats (~80 d) macaques | DDO+, S+14 d | (36) | |
| hBM-MSC | I.S.P | SOD1(G93A)dl mice (28 w) | MP+ | (37) |
| SOD1G93A mice | MP+ | (38) | ||
| mBM-MSC | I.V | SOD1G93A mice (90 d) | MP+, S+17.3 d | (39) |
| gm hBM-MSC (GDNF, VEGF, GNDF/IGF-1, BDNF) | I.M | SOD1G93A rats (80 d) | MP+, S+28 d and +18 d for GDNF, + 13 d for VEGF, +28 d for GDNF/VEGF | (40, 41) |
| mBM | I.S.P and I.M | mdf/ocd mice (6 weeks) | MP+ | (42, 43) |
| mASC | I.V | SOD1G93A mice (76–77 d) | MP+, S– | (44) |
| hASC | I.V and I.C.V | SOD1G93A mice (70 d) | MP+, DDO+, S+ | (45) |
| hUCBC | I.V | SOD1G93A mice (56 d, 66 d) | DDO+, S+21 d, +38.5 d, +23.8 d | (46–48) |
| SOD1G93A mice (60 and 90 d) | MP+, S+10 d | (49) | ||
| I.T | SOD1G93A mice | No effect | (50) | |
| I.S.P | SOD1G93A mice (40 and 90 d) | MP+, S+6 d for 40 d mice | (51) | |
| I.C.V | SOD1G93A (70 d) Wobbler mice (28 d) | MP+, S+18 d MP+ | (52) | |
| gm hUCBC (VEGF, GDNF, and/or NCAM) | I.V | SOD1(G93A)dl mice | MP+, S+ | (53, 54) |
I.P, intraperitoneal; I.M, intramuscular; I.V, intravenous; I.C.V, intracerebrovascular; I.S.P, intraspinal; I.T, intrathecal; S.C, subcutaneous; DCN, deep cerebellar nuclei; gm, genetically modified for expression of NTFs in brackets; hSC-NSC: human spinal cord-neural stem cell; m/hBM-MSC, murine/human bone marrow-mesenchymal stem cell; m/hASC, murine/human adipose derived MSC; hUCBC, human umbilical cord blood cells. Main results are summarized as follow: MP, motor performance; DDO, delay of disease onset; S, survival. The age of the model at the treatment is noted in brackets (d, days old; w, weeks). +, improvement; –, deterioration. ♂, male; ♀, female.