Table 2

Ongoing viral gene therapy clinical trials for neurological disorders

ConditionVectorAdministration routeAge of target populationStudy phaseGenetic strategy: Gene
Neurometabolic conditions
OTC deficiencyAAVIVAdultsI/IIAddition: OTC gene
AACD deficiencyAAVIPInfants, childrenIIAddition: AADC gene
MPS type 1AAVIVChildren, adolescents, adultsI/IIGene editing: insertion of IDUA gene
MPS type II (Hunters syndrome)AAVIT/IVInfants, children, adultsI/IIAddition: I2S gene (cross correction affected cells)
Gene editing: insertion of IDS gene
MPS type III (Sanfilippo disease)AAVIV/IPInfants and childrenI/II/IIIAddition: SGSH gene ± SUMF1
MPS type VIAAVIVChildren, adolescents, adultsI/IIAddition: ARSB gene
Fabry diseaseAAVIVAdultsI/IIAddition: GLA gene
Pompe diseaseAAVIV/IMChildren, adolescents, adultsIAddition: GAA gene
GSD type IIbAAVIVChildren, adolescents, adultsIAddition: LAMP2B gene
GM1 gangliosidosis type IIAAVIVChildrenI/IIAddition: GLB1 gene
Gaucher’s diseaseRetroviralIVInfants, children, adolescents, adultsIAddition: glucocerebrosidase gene, ex vivo
Diseases of the white matter
MLDLentivirus/AAVIV/IPChildrenI/IIAddition: ARSA gene, in vivo and ex vivo
ALDLentivirusIVChildren, adolescentsIIIAddition: adrenoleukodystrophy gene, ex vivo
Peripheral neuropathies
SMAAAVIVNewborns, infants, childrenIIIAddition: SMN1 gene
GANAAVITChildren, adolescents, adultsIAddition e: GAN gene
CMT1AAVIMAdolescents, adultsI/IIAddition: NFT3 gene*
Painful diabetic neuropathyHerpes virusSCAdultsIAddition GAD67 gene
Muscular dystrophies and myopathies
LGMD 2EAAVIVChildren, adolescentsI/IIAddition: SGCB gene
LGMD 2DAAVIMChildren, adolescents, adultsIAddition: a sarcoglycan gene
LGMD 2CAAVIMAdolescents, adultsIAddition: y sarcoglycan gene
X linked myotubular myopathyAAVIVInfants and young childrenI/IIAddition: hMTM1 gene
BMD/IBMAAVIMAdults BMD,
adolescents, adults IBM
Replace: follistatin gene
DMDAAVIV/IMChildren, adolescentsI/IIAddition: GALG2/mini or micro dystrophin/ follistatin genes
Neurodegenerative (central nervous system) and movement disorders
PDAAVIPAdultsIAddition: AADC/NTN*
GDFN/GABA/genes*†
HDAAVIPAdultsI/IISilence: mHTT gene
ADAAVIT/IV, IPAdultsIAddition: APOE2,
NGF, hTERT genes*
NCLAAVIP/ITInfant, child, adolescentsI/IIAddition: CLN2/CLN3/CLN6 genes
ALSLentivirus/AAVITAdultsI/IIAddition GNDF gene, ex vivo and SOD1 gene in vivo*
Neuroinflammatory diseases of the central nervous system
MSRetrovirusSCAdultsI/IIAddition: MBP gene
NMORetrovirusIVAdolescents and adultsIAddition: CD19+ and CD20+ chimeric receptor, ex vivo
  • Search strategy and selection criteria: Data for this table were identified by searches of publicly available clinical trial databases available in English that allowed systematic identification of gene therapy trials (5 February 2020); Australia and New Zealand Clinical Trials Registry (https://www.anzctr.org.au), European Union Clinical Trials Register (https://www.ema.europa.eu/en/glossary/european-union-clinical-trials-register), United Kingdom National Institute for Health Research (https://bepartofresearch.nihr.ac.uk/), United States National Library of Medicine at the NIH (clinicaltrials.gov) and Gene Therapy Clinical Trials Worldwide (http://www.abedia.com/wiley/).

  • *Neurotrophic growth factor.

  • †Neuropeptide.

  • .AACD, aromatic L-amino acid decarboxylase deficiency; AAV, adeno-associated virus; AD, Alzheimer’s disease; Adolescents, 11–19 years age; Adults, >20 years age; ALD, adrenoleukodystrophy; ALS, amyotrophic lateral sclerosis; BMD, Becker’s muscular dystrophy; Children, 1–10 years age; CMT1, Charcot Marie Tooth type 1; DMD, Duchenne muscular dystrophy; GAN, giant axonal neuropathy; GSD, glycogen storage disease; HD, Huntington’s disease; IM, intramuscular; Infants, 1–12 months age; IP, intraparenchymal; IT, intrathecal/intracisternal; IV, intravenous; LGMD, limb girdle muscular dystrophy; MLD, metachromatic leukodystrophy; MPS, mucopolysaccharidosis; MS, multiple sclerosis; NCL, neuronal ceroid lipofuscinosis; Newborns, ≤1 month age; NMO, neuromyelitis optica; OTC, ornithine transcarbamylase; PD, idiopathic Parkinson’s disease; SC, subcutaneous; SMA, spinal muscular atrophy.