Table 5 Clinical trials of engineered mitochondria in disease treatment
From: Engineered mitochondria in diseases: mechanisms, strategies, and applications
Study | Population | Sample size | Mitochondrial interventions | Administration route | Amount | main Result |
|---|---|---|---|---|---|---|
Published research | ||||||
Yu-Wai-Man323 NCT026527080 | LHON subjects carrying the m.11778G > A (MT-ND4) mutation | 37 | rAAV2/2-ND4 | Intravitreal injection | 9 × 1010 vg | 68% of subjects had a clinically relevant recovery in BCVA in at least one eye, and 78% had an improvement in vision in both eyes. |
Liu513 NCT03153293 | Patients with LHON and an MTND4m.11778G > A mutation | 149 | AAV2-ND4 | Intravitreal injection | 5 × 1011 vg | Significant improvement in visual acuity was seen within 3 days of treatment, these improvements remained stable in 12-month follow-ups. |
Yang514 NCT01267422 | Patients with LHON | 9 | rAAV2-ND4 | Intravitreal injection | 5 × 109 vg or 1 × 1010 vg | Visual function improvement was observed in both treated eyes and untreated eyes |
Yuan515 NCT01267422 | patients with the LHON mt11778G→A mutation | 9 | Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I) | Intravitreal injection | 5 × 109 vg or 1 × 1010 vg | Most patients experienced significant improvements in BCVA after treatment, with varying degrees of sustained or transient improvements over time. |
Guy516 | patients with visual loss and mutated G11778A mitochondrial DNA | 14 | Injection with the gene therapy vector AAV2(Y444,500,703F)-P1ND4v2 into one eye | Intravitreal injection | 5 × 109 vg or 2 × 1010 vg | This allotopic gene therapy for LHON at low and medium doses appears safe and does not damage the temporal peripapillary retinal nerve fiber layer |
Emani484 | Pediatric patients requiring postcardiotomy ECMO | 5 | Transplant mitochondria from autologous skeletal muscle | Direct intramyocardial injection | 1 × 108 mitochondria | 4 in 5 subjects demonstrated ventricular function improvement and separated from ECMO support. |
Guariento485 | pediatric patients requiring postcardiotomy ECMO. | MT, n = 10; Control, n = 14 | Transplant mitochondria from autologous rectus abdominis muscle | Direct epicardial injection | 1–10 × 108 mitochondria | The ratio of separation from ECMO in MT group is higher (80% VS 29%, P = 0.02) |
Jacoby486 | SLSMDs | 6 | MAT technology | Intravenously infusion | CD34+ cells were incubated with about 1 mU mitochondria | MAT decreased mtDNA heteroplasmy, and improved muscle strength and endurance in two individuals |
Ongoing research | ||||||
NCT04998357 | Cerebral ischemia | 20 | Transplant mitochondria from autologous muscle | Injection into cerebral vessels | - | - |
NCT04976140 | Refractory polymyositis or dermatomyositis | 9 | Transplant HUCSCs-derived mitochondria | Intravenous injection | - | - |
NCT05669144 | Patient candidate for CABG surgery | (MT, n = 5; Control, n = 5) | Transplant mitochondria from autologous pectoralis muscles | Intracoronary and intra-myocardial injection | - | - |
NCT02851758 | Pediatric cardiology patients on ECMO | 16 | Transplant mitochondria from autologous skeletal muscle | Direct injection into the myocardium | - | - |
NCT02652767/NCT02652780/NCT03293524 | LHON with G11778A mutation in the mitochondrial ND4 Gene | 39/37/90 | rAAV2/2-ND4 | Intravitreal injection | - | - |
