Table 3.

Pre-clinical trials in vivo in gene therapy, small molecules treatment and immunotherapy.

Animal model	Mutation/type of cells	Drug/gene delivery	Type of administration	Major findings	Reference
Charcot–Marie–Tooth disease 1 A (CMT1A)	Duplication of the PMP22/SCs	AAV2/9.shRNA Pmp22	Intra-nerve injections	A bilateral treatment restores PMP22 expression. Increased myelination and prevention of motor and sensory neuron impairments over 1 year	Gautier et al. (2021)
Charcot–Marie–Tooth disease (CMT1X) -Gjb1/Cx32 null (Cx32 KO)	Mutations in the GJB1 gene encoding a protein connexin32 (Cx32)	AAV9.Mpz.GJB1	Lumbar intrathecal injection	Improved motor functions and increased SN conduction velocities along with increased myelination and reduced inflammation in PNS	Kagiava et al. (2021)
Charcot–Marie–Tooth disease (CMT1X)-Gjb1/Cx32 null (Cx32 KO)	Mutations in the GJB1 gene encoding a protein connexin32 (Cx32)	scAAV1.tMCK.NT-3	Intramuscular delivery	Neuroprevention improved electrophysiological and histopathological phenotype of Cx32 KO mouse model	Ozes et al. (2022)
Charcot–Marie–Tooth disease type 2A (CMT2A)	Mutations in Mfn2	Small-molecule, Ser378 mimic MFN2 Ser378		A mitofusin agonist normalized axonal mitochondrial trafficking within sciatic nerves of MFN2 Thr105 → Met105 mice	Rocha et al. (2018)
Diabetic peripheral neuropathy db/db mice and human SCs (HSCs)		Cinacalcet	Standard chow diet	Cinacalcet decreased apoptosis process and increased autophagy activity after 12 weeks	Chung et al. (2018)
Diabetic neuropathy mice STZ, db/db		Inhibition of Kv2.1 by SP6616 AAV9-Kv2.1-RNAi		The results revealed the potential of SP6616 in preventing the occurrence of diabetic foot	Zhu et al. (2020)
Guillain–Barré syndrome		Anti-GM1 antibody		Anti-GM1 antibody expressed to exclusively target GM1 in either SC or axonal membranes	Goodfellow and Willison (2016)
Guillain–Barré syndrome		Inflammatory cells		Perisynaptic SCs have an important role to clear axonal debris	Cunningham et al. (2020)