Stem Cell Transplant for Age-Related Macular Degeneration

Recruiting at 1 trial location

Overseen By Emily Y Chew, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Eye Institute (NEI)

Must be taking: Immunosuppressive medications

Must not be taking: Anticoagulants, Chloroquine, Hydroxychloroquine

Disqualifiers: Uncontrolled diabetes, Chronic hepatitis, HIV, others

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

Compensation: Varies

Number of Visits: 15

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether replacing old eye cells with new ones can treat dry age-related macular degeneration, a condition causing blind spots in people over 50. Researchers focus on the safety of transplanting these cells into the eye as a potential future treatment. This involves iPSC-derived RPE/PLGA transplantation, which uses induced pluripotent stem cell-derived retinal pigment epithelium. Individuals who have experienced vision loss due to geographic atrophy and have not had "wet" macular degeneration in the affected eye might be suitable candidates. Participants will undergo specialized surgery and attend multiple follow-up visits to monitor progress.

As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking systemic anticoagulation (blood thinners) or medications with known potential toxicity to the retina, you may need to stop them. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the treatment under study is generally well-tolerated. In earlier studies, patients who received retinal cell transplants made from special stem cells did not experience serious side effects. These retinal cells are placed on a material that dissolves over time, helping them settle into the eye.

Some people have reported mild to moderate side effects, such as eye inflammation or irritation, but these are usually easy to manage. Participants in past trials responded positively without major safety issues, suggesting the treatment could be safe for humans. However, research continues to monitor any risks.

Keep in mind, this trial is in an early stage. The main goal is to ensure the treatment is safe for humans before assessing its effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for age-related macular degeneration (AMD) like anti-VEGF injections which slow vision loss, these investigational treatments use induced pluripotent stem cells (iPSCs) to regenerate retinal pigment epithelial (RPE) cells. Researchers are excited because iPSC-derived RPE cells have the potential to replace damaged cells in the retina directly, potentially restoring vision rather than just slowing deterioration. Additionally, using autologous iPSCs means the cells are derived from the patient's own body, which could reduce the risk of immune rejection. This approach represents a novel way of tackling AMD by addressing the root cause of vision loss.

What evidence suggests that this treatment might be an effective treatment for age-related macular degeneration?

Research has shown that cell transplants might help treat dry age-related macular degeneration. In earlier studies, patients received special eye cells made from their own stem cells. These transplanted cells survived in the eye and slightly improved the affected area, which is a positive sign. No serious side effects occurred, making this method seem promising. The goal is to replace damaged eye cells with healthy ones, potentially slowing or stopping vision loss. Early results are encouraging, but further research is needed to confirm these findings. Participants in this trial will receive an intervention involving autologous iPSC-derived RPE transplantation to further evaluate its effectiveness and safety. ^{1 2 4 6 7}

Who Is on the Research Team?

Emily Y Chew, M.D.

Principal Investigator

National Eye Institute (NEI)

Are You a Good Fit for This Trial?

This trial is for people over 55 with geographic atrophy from dry age-related macular degeneration, causing vision loss. Participants must have certain levels of visual acuity and be able to undergo surgery and follow-up visits. Pregnant individuals or those with 'wet' macular degeneration are excluded.

Inclusion Criteria

I am 55 years old or older.

My study eye has a specific type of retina damage and meets the vision sharpness requirements.

I have been diagnosed with AMD in at least one eye.

Exclusion Criteria

I am not willing or able to agree to participate in this or future studies.

Participant is pregnant, breast-feeding, or planning pregnancy in the first 12 months of the study

Participant actively receiving another study medication / investigational product

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for various tests

Treatment

Participants undergo retinal pigment epithelium (RPE) transplantation surgery in one eye

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including visual acuity and adverse event assessments

5 years

At least 14 visits over 5.5 years

Long-term follow-up

Participants will be contacted yearly for up to 15 years to monitor long-term safety and efficacy

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Atuologous iPSC-derived RPE on PGLA
• iPSC-derived RPE/PGLA transplantation
• iPSC-derived RPE/PLGA transplantation

Trial Overview The safety of transplanting lab-grown retinal cells into the eye is being tested as a treatment for dry age-related macular degeneration. Patients will receive these new cells through a surgical procedure in one eye, followed by extensive monitoring over several years.

How Is the Trial Designed?

Group I: Participants receiving intervention Experimental Treatment 1 Intervention

Participants receiving intervention

Atuologous iPSC-derived RPE on PGLA is already approved in United States for the following indications:

Approved in United States as Autologous iPSC-derived RPE on PLGA for:

• Geographic Atrophy Associated With Age-Related Macular Degeneration

Who Is Running the Clinical Trial?

National Eye Institute (NEI)

Lead Sponsor

Trials

572

Recruited

1,320,000+

Published Research Related to This Trial

Induced pluripotent stem cells (iPSCs) can be effectively used to create retinal pigment epithelium (RPE) cells, which are crucial for treating retinal degenerative diseases like age-related macular degeneration.

These iPSC-derived RPE cells not only resemble native RPE cells but also perform essential functions, such as metabolizing all-trans retinol, which is vital for maintaining vision, highlighting their potential for clinical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinoid Processing in Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cultures. Fields, MA., Bowrey, HE., Gong, J., et al.[2021]

Autologous human induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) cell sheets have been developed to meet clinical standards, showing characteristics similar to native RPE, such as tight junction formation and phagocytic ability.

In nonhuman primate models, these hiPSC-RPE cell sheets demonstrated safety by showing no immune rejection or tumor formation after transplantation, indicating their potential for use in treating age-related macular degeneration (AMD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Kamao, H., Mandai, M., Okamoto, S., et al.[2022]

Researchers developed clinical-grade retinal pigment epithelium (RPE) patches from induced pluripotent stem cells (iPSCs) that are free from oncogenic mutations, ensuring safer transplantation for age-related macular degeneration (AMD) patients.

The use of biodegradable scaffolds significantly enhanced the integration and functionality of these RPE patches in animal models, suggesting a promising approach for future autologous iPSC-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. Sharma, R., Khristov, V., Rising, A., et al.[2023]

Age-related macular degeneration (AMD) leads to the loss of retinal pigment epithelium (RPE) cells, which are crucial for supporting vision, and current therapies are exploring the use of pluripotent stem cells (PSCs) to replace these cells.

Early clinical trials have shown that RPE cells derived from PSCs can be safely injected or transplanted to support vision in AMD patients, indicating promising potential for cell-based therapies in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-Based Therapies for Age-Related Macular Degeneration. Khateb, S., Jha, S., Bharti, K., et al.[2021]

hiPSC-derived RPE cell sheets have been developed to replace damaged retinal pigment epithelium in age-related macular degeneration, showing characteristics similar to native RPE, such as tight junction formation and growth factor secretion.

In studies with autologous non-human primate models, these hiPSC-RPE cell sheets demonstrated safety by showing no immune rejection or tumor formation, indicating their potential for clinical use in RPE transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Study of Human Induced Pluripotent Stem Cell-derived Retinal Pigment Epithelium Cell Sheets Transplantation. Kamao, H.[2018]

Pluripotent stem cell-derived retinal pigment epithelium (RPE) shows promise as a treatment for age-related macular degeneration (AMD), with multiple manufacturing and delivery methods being explored.

While most studies focus on ensuring the safety of RPE transplants, some preliminary evidence suggests potential efficacy in improving vision for a few patients, indicating a positive direction for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet? Sharma, R., Bose, D., Maminishkis, A., et al.[2022]

A patient with advanced neovascular age-related macular degeneration successfully received a transplant of retinal pigment epithelial (RPE) cells derived from their own induced pluripotent stem cells (iPSCs), indicating the feasibility of this regenerative approach.

One year post-surgery, the transplanted RPE cell sheet remained intact, but there was no significant change in visual acuity, and cystoid macular edema was observed, suggesting that while the procedure is feasible, further improvements in efficacy are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. Mandai, M., Watanabe, A., Kurimoto, Y., et al.[2022]

Long-term transplantation of human iPSC-derived retinal pigment epithelium (iPSC-RPE) in a rat model showed initial success in preserving vision and maintaining RPE characteristics for up to 11 months, although only 50% of the transplants survived at that time.

The study identified challenges such as peri-membrane fibrosis and immune reactions that contributed to the loss of RPE monolayer characteristics over time, highlighting the need for strategies to enhance long-term graft survival and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats. Rajendran Nair, DS., Zhu, D., Sharma, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04339764

Study Details | NCT04339764 | Autologous Transplantation ... Objective: To evaluate the safety and feasibility of subretinal transplantation of iPSC-derived RPE, grown as a monolayer on a biodegradable poly lactic-co- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11526680/

Advances in retinal pigment epithelial cell transplantation for ... This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31248784/

Evaluation of Transplanted Autologous Induced Pluripotent ... The transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05445063

Study Details | NCT05445063 | Safety and Efficacy of ... This project intends to perform autologous transplantation of induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE).

5. academic.oup.com academic.oup.com/stcltm/article/13/4/317/7613343

Recent Progress in Retinal Pigment Epithelium Cell-Based ... This review summarizes recent clinical and preclinical studies involving retinal pigment epithelium transplantation as a treatment for age-related macular ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1934590924004454

Pluripotent stem-cell-derived therapies in clinical trial Here, we review the landscape of interventional hPSC trials worldwide, highlighting available data on clinical safety and efficacy.

7. insight.jci.org insight.jci.org/articles/view/179246

iPSC-RPE patch restores photoreceptors and regenerates ... Pluripotent stem cell–derived RPE transplants have been tested in early-stage clinical trials for AMD and RPE-associated monogenic diseases and ...