Stem Cell Implantation for Retinitis Pigmentosa

Overseen by David Liao, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Cedars-Sinai Medical Center

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

Disqualifiers: Glaucoma, Diabetes, Malignancies, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing if introducing special cells into the eye is safe for patients with vision loss. The cells might help protect and support the existing nerve cells in the eye, potentially slowing down or stopping vision loss.

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.

What data supports the effectiveness of the treatment CNS10-NPC, Human Neural Progenitor Cells, hNPC for Retinitis Pigmentosa?

Research shows that combining different types of stem cells, like human retinal progenitor cells and mesenchymal stem cells, can improve outcomes in retinal diseases by better maintaining eye function and reducing harmful immune responses. This suggests that using stem cells, such as those in CNS10-NPC, might be effective for treating retinal conditions like retinitis pigmentosa. ^{1 2 3 4 5}

Is stem cell implantation for retinitis pigmentosa safe?

Research shows that stem cell treatments, like human umbilical cord mesenchymal stem cells (UCMSCs), have been tested in patients with retinitis pigmentosa and found to be safe, with no serious side effects reported over a 12-month follow-up period. ^{1 6 7 8 9}

How is the treatment CNS10-NPC for retinitis pigmentosa different from other treatments?

CNS10-NPC involves the use of human neural progenitor cells, which are a type of stem cell that can potentially regenerate damaged retinal cells, offering a novel approach compared to traditional treatments that may not focus on cell regeneration. This treatment is unique because it aims to replace or repair the damaged cells in the retina, potentially restoring vision, whereas other treatments may only slow the progression of the disease. ^{1 5 6 10 11}

Research Team

David Liao, MD, PhD

Principal Investigator

Retina-Vitreous Associates Medical Group

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• CNS10-NPC (Stem Cell Therapy)

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.

Participant Groups

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)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

David E. Cohen

Cedars-Sinai Medical Center

Chief Medical Officer

MD and PhD in Physiology and Biophysics from Harvard University

Peter L. Slavin

Cedars-Sinai Medical Center

Chief Executive Officer

MD from Harvard Medical School, MBA from Harvard Business School

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Jonathan Thomas

California Institute for Regenerative Medicine (CIRM)

Chief Executive Officer

BA in Biology and History from Yale University, JD from Yale Law School, PhD in Commonwealth History from Oxford University

Rosa Canet-Avilés

California Institute for Regenerative Medicine (CIRM)

Chief Medical Officer since 2024

PhD in Neuroscience from Leeds University, BS in Organic Chemistry from Central University of Barcelona

Findings from Research

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 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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration. [2022]

3. China 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. [2020]

4. United Arab Emirates 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. [2021]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Human Retinal Progenitor Cells. [2022]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice. [2019]