Stem Cell Transplant for Age-Related Macular Degeneration

Recruiting at 1 trial location

Overseen By Ellaine M Galindez-Balut

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

Trial Summary

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.

What data supports the effectiveness of the treatment for age-related macular degeneration?

Research shows that using stem cells derived from a patient's own cells to create retinal pigment epithelium (RPE) sheets can be a promising treatment for age-related macular degeneration. These RPE sheets have shown no immune rejection or tumor formation in preclinical studies, and they mimic the function of natural RPE cells, which are crucial for eye health. ^{1 2 3 4 5}

Is the stem cell transplant for age-related macular degeneration safe?

Research shows that stem cell-derived retinal pigment epithelium (RPE) transplants, specifically using induced pluripotent stem cells (iPSCs), have not shown immune rejection or tumor formation in preclinical studies, suggesting they are generally safe for use in humans. ^{1 2 3 6 7}

How is the stem cell transplant treatment for age-related macular degeneration different from other treatments?

This treatment uses a patient's own cells, reprogrammed into stem cells, to create retinal pigment epithelium (RPE) cells, which are then transplanted to replace damaged cells in the eye. This approach is unique because it aims to restore vision by directly replacing the dysfunctional cells with healthy ones derived from the patient's own tissue, reducing the risk of immune rejection. ^{1 2 3 5 8}

What is the purpose of this trial?

Background: Age-related macular degeneration is a common eye disease in people over 50. The "dry" form of the disease can worsen into geographic atrophy, causing blind spots. Researchers want to learn if replacing older eye cells with younger ones can help treat this disease. Objective: To test the safety of putting cells inside the eye as a possible future treatment for dry age-related macular degeneration. Eligibility: People ages 55 and older who have geographic atrophy with loss of vision. People who have had "wet" macular degeneration in study eye are NOT eligible. Design: Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Eye exam * Eye photos * Fluorescein angiography. An intravenous (IV) line is placed in an arm vein. A dye is injected. A camera takes pictures of the dye as it flows through the eyes' blood vessels. * Electroretinography. An electrode is taped to participants' forehead. They sit in the dark. After 30 minutes, numbing eye drops and contact lenses are placed in their eyes. They watch flashing lights. * Tuberculosis test * Chest X-ray * Electrocardiography. Sticky pads are placed on participants' chest to record the heart's electrical activity. Participants will have at least 14 study visits over 5 and a half years. They will repeat screening tests. Participants will have retinal pigment epithelium (RPE) transplantation surgery in one eye. For this, cells from participants' blood are turned into RPE cells. These cells are placed in their eye through a cut in their retina. They will get dilating eye drops, an IV line, and anesthesia that may make them sleep. A gas bubble will be put in their eye to help it heal. Participants will receive immunosuppressive medications to avoid transplant rejection. Participants will be contacted yearly for up to 15 years.

Research Team

M. Teresa Magone de Quadros Costa, M.D.

Principal Investigator

National Eye Institute (NEI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. [2022]

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

Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

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

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

Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet? [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Retinoid Processing in Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cultures. [2021]

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

Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. [2023]

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

Cell-Based Therapies for Age-Related Macular Degeneration. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats. [2022]