Recent results of clinical studies on PD gene therapy.
| Eligibility criteria | Targeted genes and vector | Administration process | Safety/Toxicity/Efficacy | Outcome measures | Follow-up and monitoring | Clinical trials identifier and reference(s) |
|---|---|---|---|---|---|---|
| PD subjects | AADC, AAV2-hAADC | hAADC-expressing adeno-associated serotype 2 viral vectors were delivered by bilateral intra-putaminal infusions | Safe and tolerable, very few persons reported SAEs. Phase I studies | There was a significant improvement in putaminal uptake and AADC activity, and signs of dopamine signaling restoration. There is currently a clinical hold on the phase 2 VY-AADC02 project | NCT03065192/NCT03562494 [49] | |
| PD patients with mild to moderate, and moderate to severe | AADC, LV-GCH1-TH-AADC | Bilateral administration into the putamen | Safe and tolerable, but there were 3 SAEs: dyskinesia, severe psychosis, and an unidentified nervous system disorder. Every dosing cohort has a comparable safety profile. After four and six years, two deaths were reported; these were deemed to be unconnected to the treatment | In all patients, an improvement in motor score was observed. Specifically, a remarkable improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months compared with baseline | 6-month follow-up by Sio Gene Therapies | NCT00627588/NCT01856439 |
| Early PD patients | Small molecular GBA gene | Oral administration of GZ/SAR402671 | Safe and tolerable | The phase I trial was ended since its primary and secondary objectives were not achieved | NCT02906020 | |
| Idiopathic PD patients | CERE-120 (neurturin gene), AAV2-neurturin | Administered bilaterally into the substantia nigra and putamen | It was well tolerated and safe, but also caused AEs | It failed to improve the patients’ conditions | NCT00985517/NCT00400634 | |
| Advanced-stage PD patients | GAD genes, AAV-GAD | Surgical infusion into the subthalamic nucleus | It was safe and well-tolerated | UPDRS showed significant improvements in motor function | NCT00195143 [50–52] |
AADC: L-amino acid decarboxylase; AAV2-hAADC: adeno-associated virus 2-human AADC; PD: Parkinson’s disease; SAEs: serious adverse effects; LV-GCH1-TH-AADC: lentiviral-GTP cyclohydrolase 1-tyrosine hydroxylase-AADC; UPDRS: Unified Parkinson’s Disease Rating Scale; GBA: glucocerebrosidase; GAD: glutamic acid decarboxylase.
AOA: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. GOO: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. GAF: Validation, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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