Table 1.
Worldwide trials using AAV vectors against neurodegenerative disease.
| Vectors | Transgene | Disease | Phase | Patients Enrolled | Outcome | Study name | Clinicaltrail.gov | Status |
|---|---|---|---|---|---|---|---|---|
| AAV | Beta-nerve growth factor (NGF) | Alzheimer’s disease | 1 | 10 | A Phase I, Dose-Escalating Study to Assess the Safety and Tolerability of CERE-110 [Adeno-Associated Virus (AAV)-Based Vector-Mediated Delivery of Beta-Nerve Growth Factor (NGF)] in Subjects with Mild to Moderate Alzheimer’s Disease | CERE-110 in Subjects With Mild to Moderate Alzheimer’s Disease |
NCT00087789 CERE-110 2.0 × 1010 vg, CERE-110 1.0 × 1011 vg, CERE-110 2.0 × 1011 vg |
Completed |
| AAV | Beta-nerve growth factor (NGF) | Alzheimer’s disease | 2 | 49 | A Double-Blind, Placebo-Controlled (Sham Surgery), Randomized, Multicenter Study Evaluating CERE-110 Gene Delivery in Subjects with Mild to Moderate Alzheimer’s Disease | Randomized, Controlled Study Evaluating CERE-110 in Subjects With Mild to Moderate Alzheimer’s Disease |
NCT00876863 CERE-110 2.0 × 1011 vg |
Completed |
| AAV | Neurotrophic (growth) factor (Neurturin) |
Parkinson’s disease | 1/2 | 60 est/57 fact | A Phase 1/2 Trial Assessing the Safety and Efficacy of Bilateral Intraputaminal and Intranigral Administration of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) in Subjects with Idiopathic Parkinson’s Disease | Safety and Efficacy of CERE-120 in Subjects With Parkinson’s Disease |
NCT00985517 CERE-120 2.4 × 1012 vg |
Completed |
| AAV | Glutamic acid decarboxylase (GAD) | Parkinson’s disease | 1 | 12 | Phase I Study of Subthalamic GAD Gene Transfer in Medically Refractory Parkinson’s Disease | Safety Study of Subthalamic Nucleus Gene Therapy for Parkinson’s Disease | NCT00195143 | Completed |
| AAV | Glutamic acid decarboxylase (GAD) | Parkinson’s disease | 2 | 44 (est) | Phase 2 Safety and Efficacy Study Evaluating Glutamic Acid Decarboxylase Gene Transfer to Subthalamic Nuclei in Subjects with Advanced Parkinson’s Disease | Study of AAV-GAD Gene Transfer Into the Subthalamic Nucleus for Parkinson’s Disease |
NCT00643890 One-time bilateral administration of rAAV-GAD at 1 × 1012 vector genomes in 35 uL |
Terminated (Financial reasons) |
| AAV | Glutamic acid decarboxylase GAD | Parkinson’s disease | 40 est/0 fact | N/A | Long Term Follow-Up Study for rAAV-GAD Treated Subjects | NCT01301573 | Terminated (Financial reasons) |
|
| AAV | Aromatic L-amino acid decarboxylase (hAADC-2) |
Parkinson’s disease | 1 | 10 | A Phase1 Open-Label Safety Study of Intrastriatal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase (AAV-hAADC-2) in Subjects with Parkinson’s Disease [AAV-hAADC-2-003] | A Study of AAV-hAADC-2 in Subjects With Parkinson’s Disease |
NCT00229736 9 × 1010 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets 3 × 1011 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets |
Completed |
| AAV | Aromatic L-amino acid decarboxylase (hAADC-2) |
Parkinson’s disease | 1/2 | 6 est/2fact | A Phase I/II Study of Intra-Putaminal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase in Subjects with Parkinson’s Disease | AADC Gene Therapy for Parkinson’s Disease |
NCT02418598 AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) cohort 1: 3 × 1011 vg/subject cohort 2: 9 × 1011 vg/subject. |
Terminated (Another clinical study for regulatory approval is planned) |
| AAV1 | Neurotrophin factor 3 (NTF3) | Charcot–Marie–Tooth disease | 1/2a | 9est/0 fact | Phase I/II a Trial Evaluating scAAV1.tMCK.NTF3 for Treatment of Charcot–Marie–Tooth Neuropathy Type 1A (CMT1A) | Phase I/II a Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A |
NCT03520751 N = 3: intramuscular injection of (scAAV1.tMCK.NTF3) distributed bilaterally between both limbs at low dose (2 × 1012 vg/kg). N = 6: intramuscular injection of (scAAV1.tMCK.NTF3) distributed bilaterally between both limbs at low dose (6 × 1012 vg/kg) |
Not yet recruiting |
| AAV2 | Neurotrophic (growth) factor (Neurturin) |
Parkinson’s disease | 2 | 58 est/51 fact | Multicenter, Randomized, Double-Blind, Sham Surgery-Controlled Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) to Assess the Efficacy and Safety of Bilateral Intraputaminal (IPu) Delivery in Subjects with Idiopathic Parkinson’s Disease | Double-Blind, Multicenter, Sham Surgery Controlled Study of CERE-120 in Subjects With Idiopathic Parkinson’s Disease |
NCT00400634, CERE-120, bilaterally: 5.4 × 1011 vg |
Completed |
| AAV2 | Neurotrophic (growth) factor (Neurturin) |
Parkinson’s disease | 1 | 12 est | A Phase I, Open-Label Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN] to Assess the Safety and Tolerability of Intrastriatal Delivery to Subjects with Idiopathic Parkinson’s Disease | Safety of CERE-120 (AAV2-NTN) in Subjects With Idiopathic Parkinson’s Disease | NCT00252850 | Completed |
| AAV2 | Human aromatic L-amino acid decarboxylase (AADC) gene | Parkinson’s disease | 1 | 15 est/10 fact | An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion into the Putamen of Subjects with Parkinson’s Disease with Fluctuating Responses to Levodopa | Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson’s Disease (AADC) |
NCT01973543 VY-AADC01; Single dose, neurosurgically-infused, bilaterally into the striatum: 7.5 × 1011 vg, 1.5 × 1012 vg, 4.7 × 1012 vg |
Active, not recruiting |
| AAV2 | Human aromatic L-amino acid decarboxylase (AADC) gene | Parkinson’s disease | 2 | 42 est | A Randomized, Placebo Surgery Controlled, Double-Blinded, Multi-center, Phase 2 Clinical Trial, Evaluating the Efficacy and Safety of VY-AADC02 in Advanced Parkinson’s Disease with Motor Fluctuations | VY-AADC02 for Parkinson’s Disease With Motor Fluctuations |
NCT03562494, VY-AADC02 infusion, 2.5 × 1012 |
Recruiting |
| AAV2 | Human aromatic L-amino acid decarboxylase (AADC) gene | Parkinson’s disease | 50 est | An Observational, Long-Term Extension Study for Participants of Prior VY-AADC01 or VY-AADC02 Clinical Studies | Observational, Long-term, Extension Study for Participants of Prior VY-AADC01 or VY-AADC02 Studies |
NCT03733496, Participants who received VY-AADC01 or VY-AADC02 |
Enrolling by invitation | |
| AAV2 | Human CLN2 |
Late infantile neuronal ceroid lipofuscinosis (LINCL) | 1 | 11 est/10 fact | Administration of a Replication Deficient Adeno-Associated Virus Gene Transfer Vector Expressing the Human CLN2 cDNA to the Brain of Children with Late Infantile Neuronal Ceroid Lipofuscinosis | Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis |
NCT00151216 AAV2CUhCLN2, N = 5, 3 × 1012 N = 6, 3 × 1012 |
Active, not recruiting |
| AAV2 | Glial cell line-derived neurotrophic factor (GDNF) | Parkinson’s disease | 1 | 28 est/25 fact | A Phase 1 Open-Label Dose Escalation Safety Study of Convection Enhanced Delivery (CED) of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor (AAV2-GDNF) in Subjects with Advanced Parkinson’s Disease | AAV2-GDNF for Advanced Parkinson s Disease |
NCT01621581 9 × 1010 vg, 3 × 1011 vg, 9 × 1011 vg 3 × 1012 vg |
Active, not recruiting |
| AAV2 | Human ND4 | Leber’s congenital amaurosis | 3 | 90 est | Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected with G11778A ND4 Leber’s Hereditary Optic Neuropathy for Up to One Year | Safety and Efficacy Study of Gene Therapy for The Treatment of Leber’s Hereditary Optic Neuropathy |
NCT03293524, GS010, IVT eye, 9 × 1010 vg |
Active, not recruiting |
| AAV2 | Human ND4 | Leber’s congenital amaurosis | 2 + 3 | 159 est/48 fact | Safety and Efficacy Study of Gene Therapy for The Treatment of Leber’s Hereditary Optic Neuropathy |
NCT03153293, Single IVT injection, 1 × 1010 vg/0.05 mL |
Active, not recruiting | |
| AAV2 | Human ND4 | Leber’s hereditary optic neuropathy | 3 | 36 est | A Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for 6 Months or Less by LHON Due to the G11778A Mutation in the Mitochondrial ND4 Gene | Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation (RESCUE) |
NCT02652767, GS010 |
Active, not recruiting |
| AAV2 | Human ND4 | Leber’s hereditary optic neuropathy | 3 | 37 est/36 fact | Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and to 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene | Efficacy Study of GS010 for Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the ND4 Mutation (REVERSE) (REVERSE) |
NCT02652780, rAAV2/2-ND4 intravitreal, 9 × 1010 vg |
Completed |
| AAV2 | Human ND4 | Leber’s hereditary optic neuropathy | 74 est | Long-Term Follow-Up of ND4 LHON Subjects Treated with GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials | RESCUE and REVERSE Long-term Follow-up (RESCUE/REVERSE) |
NCT03406104, GS010, intravitreal injection |
Recruiting | |
| AAV2 | Human ND4 | Leber’s hereditary optic neuropathy | EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected with G11778A ND4 Leber’s Hereditary Optic Neuropathy | EAP_GS010_single Patient | NCT03672968 | Available | ||
| AAV2 | Human ND4 | Leber’s hereditary optic neuropathy | 1 | 30 est/27 fact | An Open-Label Dose Escalation Study of an Adeno-Associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber’s Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA | Safety Study of an Adeno-associated Virus Vector for Gene Therapy of Leber’s Hereditary Optic Neuropathy (LHON) |
NCT02161380 scAAV2-P1ND4v2 intravitreal: 1.18 × 109 vg 5.81 × 109 vg 2.4 × 1010 vg 1.0 × 1011 vg |
Recruiting |
| AAV9 | CLN6 | CLN6, Batten disease |
1/2a | 13 est/6 fact | Phase I/II a Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9 | Gene Therapy for Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease |
NCT02725580 AT-GTX-501 (scAAV9.CB.CLN6) |
Active, not recruiting |
| AAV9 | CLN3 | CLN3, neuronal ceroid- lipofuscinosis |
1/2a | 7 est | Phase I/II a Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis, Delivering the CLN3 Gene by Self-Complementary AAV9 | Gene Therapy for Children With CLN3 Batten Disease |
NCT03770572 AT-GTX-502 High dose Low dose |
Recruiting |
| AAV9 | Human survival motor neuron (SMN) | Spinal muscular atrophy type 1 (SMA1) | 1 | 15 est/9 fact | Phase I Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Delivering AVXS-101 | Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 |
NCT02122952 iv N = 3, 6.7 × 1013 vg/kg N = 3, 2.0 × 1014 vg/kg |
Completed |
| AAV9 | Human survival motor neuron (SMN) | SMA | 1 | 51 est/27 fact | Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting but Non-Ambulatory Patients with Spinal Muscular Atrophy | Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy (STRONG) |
NCT03381729 Intrathecal Onasemnogene abeparvovec-xioi 6.0 × 1013 vg 1.2 × 1014 vg 2.4 × 1014 vg |
Suspended |
| AAV9 | Human survival motor neuron (SMN) | Spinal muscular atrophy type 1 (SMA1) | 3 | 22est/15 fact | Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion | Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 (STR1VE) |
NCT03306277 iv Onasemnogene abeparvovec-xioi |
Completed |
| AAV9 | Human survival motor neuron (SMN) | Spinal muscular atrophy type 1 (SMA1) | 3 | 44 est/30 fact | A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants with Genetically Diagnosed and Pre-Symptomatic Spinal Muscular Atrophy with Multiple Copies of SMN2 | Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (SPR1NT) |
NCT03505099 iv, Onasemnogene abeparvovec-xioi 1.1 × 1014 vg/kg |
Active, not recruiting |
| AAV9 | Human survival motor neuron (SMN) | Spinal muscular atrophy (SMA) type 1 | 3 | 33est/30 fact | European, Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1 with One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion | Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 (STRIVE-EU) |
NCT03461289 iv Onasemnogene Abeparvovec-xioi |
Active, not recruiting |
| AAV10 | Human SGSH and SUMF1 cDNAs | Sanfilippo type A syndrome | 1 + 2 | 4 est | An Open-label, Single Arm, Monocentric, Phase I/II Clinical Study of Intracerebral Administration of Adeno-associated Viral Vector Serotype 10 Carrying the Human SGSH and SUMF1 cDNAs for the Treatment of Sanfilippo Type A Syndrome | Intracerebral Gene Therapy for Sanfilippo Type A Syndrome |
NCT01474343 Intracerebral SAF-301 |
Completed |
| AAV10 | Human SGSH and SUMF1 cDNAs | Sanfilippo type A syndrome | 1 + 2 | 4 est/ | Long-Term Follow-Up of Patient with Sanfilippo Type A Syndrome Who Have Previously Been Treated in the P1-SAF-301 Clinical Study Evaluating the Tolerability and Safety of the Intracerebral Administration of SAF-301 | Long-term Follow-up of Sanfilippo Type A Patients Treated by Intracerebral SAF-301 Gene Therapy |
NCT02053064 Intracerebral SAF-301 Long term effect |
Completed |
| AAVrh10 | Human apolipoprotein E2 (APOE2) | Alzheimer’s disease | 1 | 15 est/0 fact | Maximum Tolerated Dose of Intracisternal delivery of AAVrh.10hAPOE2 (no results) | Gene Therapy for APOE4 Homozygote of Alzheimer’s Disease |
NCT03634007 AAVrh.10hAPOE2: 8.0 × 1010 gc/kg, 2.5 × 1011 gc/kg 8.0 × 1011 gc/kg |
Recruiting |
| AAVrh10 | Human CLN2 |
Late-infantile neuronal ceroid Lipofuscinosis | 1 | 25 est/16fact | Direct CNS Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children with Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) | Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) |
NCT01161576 AAVrh10.CUhCLN2, N = 6, 9 × 1011 N = 10, 2.85 × 1011 |
Active, not recruiting |
| AAVrh10 | Human CLN2 |
Late infantile neuronal ceroid lipofuscinosis | 1 + 2 | 16 est/8 fact | Improved Results on Weill Cornell LINCL Scale and Mullen Scale (no results posted) | AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis |
NCT01414985 AAVrh10.CUhCLN2, N = 2, 9 × 1011 N = 6, 2.85 × 1011 |
Active, not recruiting |