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. Author manuscript; available in PMC: 2025 Feb 7.
Published in final edited form as: Neuron. 2019 Mar 6;101(5):839–862. doi: 10.1016/j.neuron.2019.02.017

Table 1.

Ongoing Clinical Trials Using AAV for the Treatment of CNS Diseases

Current Clinical Programs of AAV Gene Therapy in the CNS (as of October 2018)
Disease Clinical Trial phase Serotype Transgene Dose Route of administration ID ClinicalTrials.gov Sponsor References
Lysosomal storage diseases
MPS I Phase I (recruiting) AAV6 ZFN for safe insertion of hIDUA 5 × 1012 vg/kg
1 × 1013 vg/kg
5 × 1013 vg/kg		 Intravenous NCT02702115 Sangamo Therapeutics Harmatz et al., 2018
MPS II Phase I (recruiting) AAV6 ZFN for safe insertion of hIDS 5 × 1012 vg/kg
1 × 1013 vg/kg
5 × 1013 vg/kg		 Intravenous NTC03041324 Sangamo Therapeutics Laoharawee et al., 2018
MPS IIIA Phase I/II (recruiting) AAV9 hSGSH 0.5 × 1013 vg/kg
1 × 1013 vg/kg
3 × 1013 vg/kg		 Intravenous NCT02716246 Abeona Therapeutics N/A
Phase II/III (recruiting) AAVrh.10 hSGSH 7.2 × 1012vg total
over 6 sites		 Intracerebral NCT03612869 LYSOGENE Tardieu et al., 2014
MPSIIIB Phase I/II (active, not recruiting) AAV5 hNAGLU 4 × 1012 vg total
over 16 sites		 Intracerebral NCT03300453 UniQure Biopharma B.V. Ellinwood et al., 2011
Phase I/II (recruiting) AAV9 hNAGLU 2 × 1013 vg/kg
5 × 1013 vg/kg		 Intravenous NCT03315182 Nationwide Children’s Hospital N/A
LINCL (Batten disease) Phase I (active, not recruiting) AAV2 hCLN2 3 × 1012 vg total
over 12 sites		 Intraparenchymal NCT00151216 Weill Medical College of Cornell University Worgall et al., 2008
Phase I/II (active, not recruiting) AAVrh.10 hCLN2 9.0 × 1011 vg total
2.85 × 1011 vg total
over 12 sites		 Intraparenchymal NCT01161576 and NCT01414985 Weill Medical College of Cornell University N/A
Phase I/II (recruiting) AAV9 hCLN3 Not disclosed (“low” and ‘‘high’’ doses) Intrathecal NCT03770572 Nationwide Children’s Hospital N/A
Phase I/II (recruiting) AAV9 hCLN6 1.5 × 1013 vg Intrathecal NCT02725580 Nationwide Children’s Hospital N/A
MLD Phase I/II (active, not recruiting) AAVrh.10 hARSA 1 × 1012 vg total
4 × 1012 vg total
over 12 sites		 Intraparenchymal NCT01801709 Institut National de la Santé et de la Récherche Medicale, France Colle et al., 2010; Zerah et al., 2015
Hereditary leukodystrophy
Canavan disease Phase 1 recruiting AAV2 hASPA 9 × 1011 vg over six sites Intraparenchymal NA National Institute of Neurological Disorders and Stroke Leone et al., 2012
Neurotransmitter disorder
AADC deficiency Phase I/II (active, not recruiting) AAV2 hAADC Not disclosed Intraparenchymal (Putamen) NCT01395641 National Taiwan University Hospital Hwu et al., 2012; Chien et al., 2017
Phase II (recruiting) - expansion of NCT01395641 AAV2 hAADC 2.37 × 1011 vg total Intraparenchymal (putamen) NCT02926066 National Taiwan University Hospital
Phase I (recruiting) AAV2 hAADC 1.3 × 1011 vg total Intraparenchymal (SNc and VTA) NCT02852213 University of California, San Francisco
Idiopathic age-related neurodegenerative diseases
Parkinson’s disease Phase I/II (active, not recruiting) AAV2 NTN 2.4 × 1012 vg total
over 4 sites sham surgery		 Intraparenchymal (putamen and SNc) NCT00985517 Sangamo Therapeutics Marks et al., 2010
Phase I (active, not recruiting) AAV2 hGDNF 9 × 1010 vg total
3 × 1011 vg total
9 × 1011 vg total
3 × 1012 vg total		 Intraparenchymal + CED (putamen) NCT01621581 National Institute of Neurological Disorders and Stroke (NINDS) Johnston et al., 2009; Su et al., 2009
Phase I (active, not recruiting) AAV2 hAADC 7.5 × 1011 vg total
1.5 × 1012 vg total
4.7 × 1012 vg total		 Intraparenchymal (striatum) NCT01973543 Voyager Therapeutics Bankiewicz et al., 2006
Phase II (recruiting) AAV2 hAADC 2.5 × 1012 vg total
versus sham		 Intraparenchymal (striatum) NCT03562494 Voyager Therapeutics
Phase I (active, not recruiting) AAV2 hAADC 9.4 × 1012 vg total Intraparenchymal (striatum) NCT03065192 Voyager Therapeutics
Phase I/II (recruiting) AAV2 hAADC 3 × 1011 vg total
9 × 1011 vg total
over 4 sites		 Intraparenchymal (putamen) NCT02418598 Jichi Medical University Christine et al., 2009
Alzheimer’s disease Phase I AAV2 hNGF 8.0 × 1010 vg total
2.5 × 1011 vg total
8.0 × 1011 vg total		 Intraparenchymal (basal forebrain region) NCT00087789 Ceregene Rafii et al., 2014, 2018
Phase I (not yet recruiting) AAVrh.10 hAPOE2 8.0 × 1010 gc/kg
2.5 × 1011 gc/kg
8.0 × 10-gc/kg		 Intracisternal NCT03634007 Weill Medical College of Cornell University Rosenberg et al., 2018
Spinal cord disorders
SMA1 Phase I (recruiting) AAV9 SMN 6.0 × 1013 vg total
1.2 × 1014 vg total		 Intrathecal NCT03381729 AveXis N/A
Phase III (recruiting) AAV9 SMN 1.1 × 1014 vg/kg Intravenous NCT03505099 AveXis Mendell et al., 2017
Phase III (active, not recruiting) AAV9 SMN Not disclosed Intravenous NCT03306277 AveXis
Phase III (recruiting) AAV9 SMN Not disclosed Intravenous NCT03461289 AveXis

Active clinical interventional AAV studies listed on https://clinicaltrials.gov as of October 2018 are included while completed or terminated studies are not listed. Associated references correspond either to studies demonstrating the proof of concept of a strategy in animal models other than mice or to clinical results in patients already published.

Abbreviations: MPS, Mucopolysaccharidosis; LINCL, late infantile neuronal ceroidlipofuscinosis; MLD, metachromatic leukodystrophy; IDUA, alpha-L-iduronidase; IDS, iduronate2-sulfatase; SGSH, N-sulfoglucosamine sulfohydrolase; NAGLU, alpha-N-acetylglucosaminidase; ARSB, arylsulfatase B; CLN2, protein tripeptidyl peptidase-l; AADC, aromatic L-amino-acid decarboxylase; NTN, neurturin; GDNF, glial-cell-derived neurotrophic factor; NGF, nerve growth factor; APOE2, apolipoprotein 2; SMA1, spinal muscular atrophy type 1; SMN1, survival motor neuron 1; SNc, substantia nigra pars compacta; VTA, ventral tegmental area.