Stem Cell Implantation for Retinitis Pigmentosa

Overseen By Pablo Avalos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Oral retinoids, Immunosuppressants, Corticosteroids, others

Disqualifiers: Glaucoma, Diabetes, Malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new stem cell treatment, CNS10-NPC, for individuals with Retinitis Pigmentosa (RP), a condition that causes vision loss. Researchers aim to determine the safety of transplanting these specialized cells into the eye to potentially aid the condition. Different groups in the trial receive varying doses of the treatment to assess their responses. Individuals diagnosed with RP and vision worse than 20/80 might be suitable candidates for this study. As a Phase 1 trial, participants will be among the first to receive this innovative treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are on certain medications like systemic corticosteroids, immunosuppressants, or specific oral retinoids. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that CNS10-NPC cells are likely to be safe for humans?

Research has shown that CNS10-NPC cells have been tested in animals without causing harm. These stem cells were injected into animals, and no negative effects occurred. The animals maintained stable body weight and showed no organ problems.

This trial is in its early stages, focusing on assessing the treatment's safety for humans. Although the treatment has shown promise in animals, its safety in people is still under investigation.

Overall, the animal studies provide some confidence, but human trials like this one are essential to determine the treatment's safety for people with Retinitis Pigmentosa. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for retinitis pigmentosa, which often focus on managing symptoms or slowing progression, CNS10-NPC is a cutting-edge stem cell therapy aimed at repairing and regenerating damaged retinal cells. This treatment is delivered directly into the eye through a subretinal injection, potentially offering a more direct and effective approach to restoring vision. Researchers are particularly excited about CNS10-NPC because it harnesses the regenerative power of stem cells, which could open new pathways for not just halting vision loss but actually improving visual acuity in patients with this degenerative condition.

What evidence suggests that CNS10-NPC might be an effective treatment for Retinitis Pigmentosa?

Research has shown that CNS10-NPC cells might slow vision loss in animal studies. These special cells, capable of transforming into various nerve cell types, are injected into the eye to potentially address vision problems. In these studies, the cells caused no harm, suggesting safety. They aim to become supportive cells in the nervous system, potentially protecting and repairing eye cells. In this trial, participants will receive a single, unilateral, subretinal injection of CNS10-NPC cells. Although this treatment has not yet been tested in humans, early animal research offers hope that it could help people with Retinitis Pigmentosa by slowing or stopping vision loss. ^{1 2 3 4 6}

Who Is on the Research Team?

David Liao, MD, PhD

Principal Investigator

Retina-Vitreous Associates Medical Group

Are You a Good Fit for This Trial?

Adults diagnosed with Retinitis Pigmentosa (RP) who have visual acuity of 20/200 or worse, or a central visual field of 40 degrees diameter or less. They must be able to undergo eye surgery and sign informed consent. Excluded are those on certain medications, with allergies to specific antibiotics, recent substance abuse, ocular abnormalities that could affect the study's outcome, systemic diseases affecting ocular function, pregnant/nursing women, and unwillingness to use contraception.

Inclusion Criteria

I am medically cleared for eye surgery.

Subject must understand and sign the protocol's informed consent

Waxy disc pallor

Exclusion Criteria

I agree to use contraception for at least 6 months after surgery.

I have not had a serious illness or infection in the last 28 days.

History of any investigational agent administration within 28 days prior to administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single, unilateral, subretinal injection of CNS10-NPC cells

1-2 weeks

1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits over 12 months

Long-term follow-up

Participants are monitored for long-term safety and retinal changes

15 months

5 visits over 15 months

What Are the Treatments Tested in This Trial?

Interventions

• CNS10-NPC

Trial Overview The trial is testing the safety of implanting CNS10-NPC cells into the subretinal space in RP patients. These neural progenitor cells are designed to become astrocytes in hopes of treating RP. This is an initial human test following animal studies.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

Visual acuity between 20/80 and 20/200 Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=10)

Group II: Group 1B Experimental Treatment 1 Intervention

Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=3)

Group III: Group 1A Experimental Treatment 1 Intervention

Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 300,000 CNS10-NPC (n=3)

CNS10-NPC is already approved in United States for the following indications:

Approved in United States as CNS10-NPC for:

• Retinitis Pigmentosa (under investigation)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

Human retinal progenitor cells (hRPC) were found to be safe and effective in preserving visual function and retinal structure in dystrophic rats, with optimal doses identified between 50,000 to 100,000 cells.

The study revealed that hRPC integrated well into the retina without causing tumors or adverse effects, and highlighted that dexamethasone treatment could negatively impact visual acuity, which is crucial for interpreting results in cell transplant studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Human Retinal Progenitor Cells. Semo, M., Haamedi, N., Stevanato, L., et al.[2022]

In a phase I/II clinical trial involving 32 advanced retinitis pigmentosa (RP) patients, intravenous administration of human umbilical cord mesenchymal stem cells (UCMSCs) was found to be safe, with no serious adverse effects reported over a 12-month follow-up.

Most patients experienced improvements in their best corrected visual acuity (BCVA) within the first 3 months, with 81.3% maintaining or improving their visual function throughout the year, indicating that UCMSCs may offer a promising therapeutic option for advanced RP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells Maintains and Partially Improves Visual Function in Patients with Advanced Retinitis Pigmentosa. Zhao, T., Liang, Q., Meng, X., et al.[2021]

Pre-induced adult human peripheral blood mononuclear cells (hPBMCs) successfully survived and migrated within the retina for at least three months after being transplanted into a mouse model of retinitis pigmentosa, indicating their potential for cell replacement therapy.

The transplanted hPBMCs expressed key human neuronal and photoreceptor markers, suggesting they could contribute to retinal repair and function in degenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and migration of pre-induced adult human peripheral blood mononuclear cells in retinal degeneration slow (rds) mice three months after subretinal transplantation. Peng, Y., Zhang, Y., Huang, B., et al.[2021]

In a phase 3 clinical study involving 82 patients with retinitis pigmentosa, the implantation of 5 million umbilical cord-derived mesenchymal stem cells (UC-MSCs) into the suprachoroidal area showed significant improvements in best corrected visual acuity (BCVA) and visual field (VF) over a 6-month follow-up period, indicating its efficacy.

The procedure was found to be safe, with no serious ocular or systemic complications reported, suggesting that UC-MSC therapy could be a promising treatment for degenerative retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord derived mesenchymal stem cell implantation in retinitis pigmentosa: a 6-month follow-up results of a phase 3 trial. Kahraman, NS., Oner, A.[2020]

Photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells can successfully differentiate into functional photoreceptors after transplantation into mice with retinal degeneration, indicating their potential for treating conditions like retinitis pigmentosa.

Visual function in treated mice was partially restored, with improvements correlating positively with the number of transplanted cells, demonstrating the efficacy of stem cell-derived therapies for retinal repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice. Barnea-Cramer, AO., Wang, W., Lu, SJ., et al.[2019]

In a 10-month study involving 5 patients with advanced retinitis pigmentosa or cone-rod dystrophy, a single intravitreal injection of autologous bone marrow-derived mononuclear cells showed no adverse events, indicating a good safety profile for this treatment.

Four out of five patients experienced a 1-line improvement in best-corrected visual acuity shortly after the injection, suggesting potential efficacy, although further research is needed to fully understand the benefits of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Siqueira, RC., Messias, A., Voltarelli, JC., et al.[2022]

Transplanting a combination of human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) into the subretinal space of RCS rats resulted in better maintenance of retinal function, as shown by improved electroretinogram results compared to single cell type transplants.

The combined transplantation not only enhanced the thickness of the outer nuclear layer and photoreceptor differentiation but also showed superior immunomodulatory effects by effectively suppressing microglial activation and Müller cell gliosis, making it a promising strategy for treating retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats. Qu, L., Gao, L., Xu, H., et al.[2018]

Human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) showed long-term functional rescue in animal models of retinal degeneration, sustaining visual function for over 220 days without causing teratoma formation.

In a Good Laboratory Practice-compliant study, hESC-RPE transplantation in immune-deficient mice demonstrated no evidence of tumor formation, indicating a promising safety profile for potential clinical applications in treating retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Lu, B., Malcuit, C., Wang, S., et al.[2022]

In a study using the Royal College of Surgeons rat model, umbilical tissue-derived cells were found to significantly preserve photoreceptor integrity and visual functions, outperforming other cell types like placenta-derived and mesenchymal stem cells.

The umbilical-derived cells not only provided extensive photoreceptor rescue but also showed no signs of tumor formation or harmful side effects, suggesting they could be a safe and effective treatment option for retinal degenerative diseases like retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Lund, RD., Wang, S., Lu, B., et al.[2022]

Human embryonic stem cell-derived retinal tissues (hESC-retina) successfully integrated and differentiated into various retinal cell types, including photoreceptors, in animal models, indicating their potential for effective transplantation therapy.

The study established new primate models of retinal degeneration and demonstrated the feasibility of hESC-retina transplantation, paving the way for future clinical applications in treating conditions like retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration. Shirai, H., Mandai, M., Matsushita, K., et al.[2022]

In a phase I study involving 3 patients with advanced retinitis pigmentosa, the intravitreal injection of autologous bone marrow mesenchymal stem cells (MSCs) was found to be safe for 2 out of 3 patients, who experienced improvements in light perception without adverse effects.

However, one patient developed severe complications, including fibrous tissue proliferation and tractional retinal detachment, indicating that while MSC therapy shows potential, it poses significant safety risks that need to be addressed before further clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study. Satarian, L., Nourinia, R., Safi, S., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04284293

NCT04284293 | CNS10-NPC for the Treatment of RP Obtain evidence that subretinal injection of CNS10-NPC can favorably impact the progression of vision loss in subjects with moderate RP. Official Title.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10519102/

GMP-grade human neural progenitors delivered subretinally ... Injection of CNS10-NPC did not affect animals' physiology, and no adverse responses were detected in body weight and weight from multiple organs ...

3. cirm.ca.gov cirm.ca.gov/our-progress/awards/clinical-study-assess-safety-and-efficacy-subretinal-injection-human-neural-progenitor-cells-treatment-retinitis-pigmentosa/

Clinical Study to Assess Safety and Efficacy of Subretinal ... Clinical Study to Assess Safety and Efficacy of Subretinal Injection of Human Neural Progenitor Cells for Treatment of Retinitis Pigmentosa · Grant Award Details.

4. biorxiv.org biorxiv.org/content/10.1101/2025.01.06.631620v1.full-text

Dynamic Transcriptomic Remodeling in Human Neural ... Human neural progenitor cells (hNPCs) have shown promise in slowing down retinal degeneration in animal models and are currently being tested in ...

5. trialx.com trialx.com/clinical-trials/listings/221085/cns10-npc-for-the-treatment-of-rp/

CNS10-NPC for the Treatment of RP This study will be the first to use a human progenitor cell line to treat retinitis pigmentosa in people. This is a Phase 1/2a, single-center, open label, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5622579/

Long-term safety of human retinal progenitor cell ... Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa.