Transplanted Neural Progenitor Cells Survive One Year in Retinitis Pigmentosa Patients, Phase 1/2a Trial Shows
核心洞察
Transplanted human neural progenitor cells (CNS10-NPC) survived for at least one year following subretinal transplantation in 13 patients with retinitis pigmentosa (搜索), with a favorable safety profile.
The Phase 1/2a trial, funded by CIRM, represents the first demonstration of long-term engraftment of fetal-derived neural progenitor cells in RP patients, a critical milestone for stem cell-based retinal therapies.
Visual acuity remained stable throughout the 12-month study, and OCT imaging confirmed persistent transplanted cells in the subretinal space; cell-related adverse events included three epiretinal membranes and one persistent subretinal bleb.
A Phase 1/2a clinical trial evaluating CNS10-NPC, a human neural progenitor cell product, has demonstrated that transplanted cells survive for at least one year following subretinal injection in patients with retinitis pigmentosa (搜索) (RP), while maintaining a favorable safety profile. The previously unpublished data were presented at ISSCR 2026 by Clive Svendsen, Ph.D., of the Cedars-Sinai Board of Governors Regenerative Medicine Institute (搜索).
The study, funded by the California Institute for Regenerative Medicine (搜索) (CIRM), enrolled 13 patients with RP who received a single subretinal injection of either 300,000 or 1,000,000 cells. Participants were followed for 12 months and subsequently enrolled into a long-term follow-on protocol.
"This study represents the first demonstration of long-term survival of fetal-derived neural progenitor cells in patients with retinitis pigmentosa (搜索) while maintaining a favorable safety profile," said Svendsen. "Long-term engraftment is a critical milestone for the development of stem cell-based therapies for retinal disease and provides an important foundation for future studies."
Safety and Engraftment Outcomes
Visual acuity remained stable throughout the 12-month study period, and optical coherence tomography (OCT) imaging confirmed that transplanted cells remained present in the subretinal space for at least one year. Cell-related adverse events included three epiretinal membranes and one persistent subretinal bleb. Overall, investigators concluded that the treatment was well tolerated and resulted in long-term cell engraftment.
Because RP progresses slowly, changes in vision were not expected during the first year. Investigators continue to follow participants to determine whether long-term survival of the transplanted cells can help preserve vision in the treated eye over time.
"Our goal is to help patients maintain their vision for as long as possible," said Dr. Liao, the clinical lead on the project. "The next critical question is whether these surviving cells can slow the continued deterioration that occurs in retinitis pigmentosa (搜索)."
A Mutation-Independent Strategy
Unlike gene therapies that target individual mutations — such as the approved RPE65 gene therapy — neural progenitor cell transplantation is designed as a mutation-independent strategy. Retinitis pigmentosa (搜索) is linked to more than 80 genes with over 3,000 mutations, making mutation-specific approaches challenging for the broader patient population. Cell-based therapies offer the potential for a gene-agnostic approach that could benefit a broader population.
Preclinical studies demonstrated that CNS10-NPC preserved photoreceptors and vision in animal models through reducing inflammation and the release of powerful growth factors, supporting its evaluation in patients.
Mechanistic Insights from Preclinical Research
Concurrently, a comprehensive preclinical study published in Nature Communications has elucidated the molecular mechanisms underlying hNPC-mediated retinal protection and the temporal dynamics of graft-host interactions. Using single-cell RNA sequencing (scRNA-seq) in the Royal College of Surgeons (RCS) rat model of retinal degeneration, researchers identified 14 transcriptomically distinct hNPC subpopulations and demonstrated that grafted hNPCs predominantly adopt an astrocytic fate and gradually mature over time within the host retinal environment.
The study identified key trophic factors expressed by hNPCs, including mesencephalic astrocyte-derived neurotrophic factor (MANF), myeloid-derived growth factor (MYDGF (搜索)), midkine (MDK (搜索)), and pleiotrophin (PTN (搜索)). Notably, MANF signaling emerged as a key mechanism underlying hNPC-mediated retinal protection, contributing to photoreceptor survival, immune modulation, and inflammation control.
Grafted hNPCs protected vision through multiple modalities, including trophic factor release, extracellular matrix (ECM) remodeling, metabolic regulation, and suppression of apoptosis, oxidative stress, and inflammation. The host retina showed temporal changes in phototransduction, visual perception, glial responses, and metabolic processes.
The Challenge of Durability
A critical finding from the preclinical work was that signaling interactions and communication strength between hNPCs and host retinal cells declined over time. At P60, trophic factor (MANF, FGF, BMP), synaptic (NRXN, NCAM), and cell adhesion signaling pathways were highly upregulated, ensuring trophic support, synaptic stability, and ECM integrity. By P90, these pathways were significantly downregulated, reflecting a progressive decline in neuroprotective support.
"These findings highlight the central importance of the host retinal environment in supporting graft survival and function, underscoring the need to pair stem cell therapy with strategies that fortify the host retina to sustain long-term vision preservation," the authors noted.
ERG b-wave amplitudes remained significantly higher for hNPC-treated eyes compared to untreated controls at P60 and P90, indicating preservation of cone and inner retinal activity. However, while visual acuity for hNPC-treated eyes remained significantly higher than untreated controls and stable over time, ERG b-wave amplitudes decreased from P60 to P90, reflecting progressive decline of retinal function.
Future Directions
Svendsen also presented data on an induced pluripotent stem cell (iPSC)-derived neural progenitor product during the ISSCR presentation. An iPSC-based approach could provide a more scalable therapy capable of treating substantially more patients in the future while avoiding ethical concerns associated with fetal tissue sources.
The preclinical researchers emphasized that combining hNPC therapy with interventions targeting synaptic support mechanisms in the early degeneration stage and immune modulation in the later stage may be critical for optimizing vision preservation. They also highlighted the potential of genetically engineered hNPCs with enhanced MANF secretion as a promising therapeutic strategy for long-term photoreceptor survival and function.
The clinical trial is registered as NCT04284293.