Cell therapy weekly: updates from ESGCT 2025
At the European Society of Gene & Cell Therapy (ESGCT) 32nd annual congress (Seville, Spain; 7-10 October 2025) Genethon (Paris France) gave updates on its Duchenne muscular dystrophy gene therapy trial, JCR Pharmaceuticals (Hyogo, Japan) presented research on its JUST-AAV capsid engineering platform, and Neurogene (NY, USA) presented preclinical research supporting its choice of delivery method for its Rett syndrome gene therapy.
The news highlights:
- Long-term Duchenne gene therapy efficacy results
- Improved AAV targeting to central nervous system and muscle
- Preclinical data and regulatory updates for Rett syndrome gene therapy
Long-term Duchenne gene therapy efficacy results
Genethon announced positive two-year efficacy results from its Phase I/II dose escalation trial investigating GNT0004, an AAV8-based gene therapy for Duschenne muscular dystrophy.
Patients who received GNT0004 demonstrated substantial clinical improvements compared to untreated patients. Participants showed meaningful gains in motor function and faster movement times, including improved ability to rise from the floor and increased walking speed over measured distances. The effectiveness was also demonstrated by reductions in creatine phosphokinase, a biomarker of muscle damage, decreasing by 75% at 18 months and remaining reduced by 61% after two years.
The therapy maintained its safety profile throughout the study period, with no serious adverse events reported. These encouraging results support Genethon’s decision to advance to Phase 3 trials, which are currently enrolling 64 ambulatory boys aged 6-10 using the same therapeutic dose.
Improved AAV targeting to central nervous system and muscle
JCR Pharmaceuticals presented breakthrough research on its JUST-AAV capsid engineering platform, demonstrating significant advances in targeted gene therapy delivery. The proprietary technology addresses major challenges in treating central nervous system and muscle disorders by improving precision while reducing unwanted side effects.
The platform’s key innovation lies in its ability to deliver therapeutic agents more efficiently to specific target tissues compared to conventional AAV9 vectors. Their presentation at the ESGCT Congress also reported on preclinical studies involving mice and monkeys. Results showed that the engineered capsids achieved dramatically enhanced muscle transduction – up to 28-fold higher in quadriceps and 52-fold higher in heart tissue. Simultaneously, the technology reduced liver exposure by 160-fold, addressing a critical safety concern in gene therapy.
The JUST-AAV system incorporates specialized targeting mechanisms, including J-Brain Cargo® for central nervous system delivery and novel muscle-targeting peptides identified through extensive screening. The team also successfully developed dual-targeting variants that can simultaneously reach both brain and muscle tissues with comparable efficiency to single-target versions.
Preclinical data and regulatory updates for Rett syndrome gene therapy
Neurogene has completed regulatory discussions with the FDA regarding its pivotal Embolden registrational trial, studying NGN-410 gene therapy for Rett syndrome. The company plans to begin patient dosing in the fourth quarter of 2025 across 13 clinical sites.
New preclinical research presented at the ESCGT Congress provides compelling evidence supporting Neurogene’s chosen delivery method for NGN-401. The study compared intracerebroventricular (ICV) administration against intrathecal lumbar (IT-L) delivery in nonhuman primates, demonstrating that ICV delivery achieves superior distribution of the therapeutic gene across brain regions critical to Rett syndrome pathology.
The comparative study revealed that ICV administration produced higher levels of therapeutic MECP2 gene expression in key brain areas compared to equivalent doses delivered via IT-L. Even when researchers tested IT-L delivery at approximately four times the standard clinical dose, ICV administration still demonstrated superior brain penetration. Importantly, both delivery methods showed comparable exposure to peripheral organs including the liver, indicating that IT-L offers no protective advantage for liver safety.
These preclinical findings provide scientific rationale for the encouraging clinical results previously observed in Neurogene’s Phase 1/2 trial, where the first four participants demonstrated acquisition of 23 developmental milestones across multiple functional domains.