Table 1.
AAV-mediated gene therapy in clinical trials for neurodegenerative diseases in the central nervous system
| Disease | Therapeutic gene | Serotype | Administration | Number of patients | Identifier | Clinical trial phase & Status | Remarks |
|---|---|---|---|---|---|---|---|
| Parkinson’s disease | GDNF | AAV2 | Putaminal | 25 | NCT01621581 | Phase I, active not recruiting | Convection-enhanced delivery method was performed to infuse virus vectors into the brain |
| NTN/CERE-120 | AAV2 | Substantia nigra and putamen | 60* | NCT00985517 | Phase I/II, active not recruiting | No difference was observed between AAV2-NTN-treated and sham-operated patients | |
| GAD | AAV2 | Subthalamic nucleus | 45 | NCT00643890 | Phase II, terminate | AAV2-GAD gene therapy improved UPDRS motor score at 6 months | |
| AADC | AAV2 | Intraputaminal | 10 | NCT00229736 | Phase I, complete | AAV2-AADC treatment was safe and that AADC gene expression was maintained at least 4 years after administration of therapy | |
| AADC | AAV2 | Intraputaminal | 6* | NCT02418598 | Phase I/II, active recruiting | Evaluating the safety, efficacy of intraputaminal administration of AAV2-AADC by stereotaxic surgery in advanced PD patients | |
| Alzheimer’s disease | APOE2 | AAVrh.10 | Intracisternal | 15* | NCT03634007 | Phase I, active not recruiting | The study will explore a maximum dose and attempt to convert APOE4 homozygotes to APOE2-APOE4. |
| NGF/CERE-110 | AAV2 | Basal forebrain | 49 | NCT00876863 | Phase II, active not recruiting | AAV-NGF had no benefit on cognition at 24 months after treatment | |
| Canavan disease | ASPA | AAV2 | Intraparenchymal | 21 | McPhee et al., 2006; Leone et al., 2012 | Phase I, complete | The gene therapy was tolerable with no severe adverse effects and delayed progression of brain atrophy |
| Spinal muscular atrophy | AVXS-101 | AAV9 | Intravenous | 15 | NCT02122952 | Phase I, complete | The study prolonged survival, improved motor function, and increased the CHOP INTEND scores |
| AVXS-101 | AAV9 | Intravenous | 44* | NCT03505099 | Phase III, active recruiting | This study will recruit patients with multiple copies of SMN2 | |
| Metachromic leukodystrophy | Arylsulfatase A | AAVrh.10 | Intracerebral | 5* | NCT01801709 | Phase I/II, active not recruiting | Safety and efficacy evaluated based on clinical, neuropsychological, radiological, electrophysiological and biological parameters |
*Estimated number of enrolled participants. AAV: Adeno-associated virus; GDNF: glial cell line-derived neurotrophic factor; NTN: neurturin; CERE: Ceregene; GAD: glutamic acid decarboxylase; UPDRS: unified PD rating scale; AADC: aromatic L-amino acid decarboxylase; PD: Parkinson’s disease; APOE: apolipoprotein E; NGF: nerve growth factor; ASPA: aspartoacylase; AVXS-101: AveXis-101; CHOP INTEND: Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; SMN2: survival motor neuron 2.