Stem Cell Transplant for Age-Related Macular Degeneration
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Trial Summary
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.
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.
12345Is 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.
12367How 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.
12358Eligibility 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.
+4 more
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
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Participants receiving interventionExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins UniversityBaltimore, MD
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Eye Institute (NEI)Lead Sponsor
References
Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. [2022]We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).
Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. [2022]Age-related macular degeneration (AMD) causes severe visual impairment due in part to age-dependent impairment of retinal pigment epithelium (RPE). It has been suggested that autologous human induced pluripotent stem cells (hiPSCs) may represent a useful cell source for the generation of graft RPE. We generated hiPSC-derived RPE (hiPSC-RPE) cell sheets optimized to meet clinical use requirements, including quality, quantity, consistency, and safety. These cell sheets are generated as a monolayer of cells without any artificial scaffolds, express typical RPE markers, form tight junctions that exhibit polarized secretion of growth factors, and show phagocytotic ability and gene-expression patterns similar to those of native RPE. Additionally, upon transplantation, autologous nonhuman primate iPSC-RPE cell sheets showed no immune rejection or tumor formation. These results suggest that autologous hiPSC-RPE cell sheets may serve as a useful form of graft for use in tissue replacement therapy for AMD.
Preclinical Study of Human Induced Pluripotent Stem Cell-derived Retinal Pigment Epithelium Cell Sheets Transplantation. [2018]Age-related macular degeneration is one of the leading causes of blindness characterized by progressive dysfunction of retinal pigment epithelium (RPE) and RPE transplantation. The replacement of pathological RPE with healthy RPE, is being investigated for AMD treatment. In recent years increasing attention has been given to human induced pluripotent stem cells (hiPSCs) as a useful cell source for RPE transplantation. We generated hiPSC-derived RPE (hiPSC-RPE) cell sheets optimized to meet clinical use requiring efficacy, consistency, and safety. These grafts consist of a monolayer of cells without any artificial scaffolds, and express typical RPE markers, form tight junctions that exhibit polarized secretion of growth factors, and show phagocytotic ability and gene expression patterns similar to those of native RPE. Additionally, autologous non-human primate iPSC-RPE cell sheets showed no immune rejection or tumor formation. These results suggest that autologous hiPSC-RPE cell sheets may serve as a useful cell source for RPE transplantation.
Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet? [2022]Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD.
Retinoid Processing in Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cultures. [2021]Stem cell therapy for retinal degenerative diseases such as age-related macular degeneration is a promising clinical option for the replacement of photoreceptors and retinal pigment epithelium (RPE). Induced pluripotent stem cell technology has emerged as a viable potential source of cells for transplantation in retinal degenerative disorders. Induced pluripotent stem cells have been used to derive RPE and have been tested for their functional behavior. These cells have the ability to express RPE-specific proteins and morphologically resemble native RPE. Induced pluripotent stem cell-derived RPE are also able to contribute to the visual cycle by their ability to metabolize all-trans retinol, a critical function of RPE in maintaining visual function. Advances in induced pluripotent stem cell technology will contribute to the development of clinical therapies for retinal degenerative diseases as well as provide a tool to understand the pathology of these disorders.
Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. [2023]Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.
Cell-Based Therapies for Age-Related Macular Degeneration. [2021]Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. The pathogenesis of AMD involves dysfunction and loss of the retinal pigment epithelium (RPE), a monolayer of cells that provide nourishment and functional support for the overlying photoreceptors. RPE cells in mammals are not known to divide, renew or regenerate in vivo, and in advanced AMD, RPE loss leads to degeneration of the photoreceptors and impairment of vision. One possible therapeutic approach would be to support and replace the failing RPE cells of affected patients, and indeed moderate success of surgical procedures in which relatively healthy autologous RPE from the peripheral retina of the same eye was transplanted under the retina in the macular area suggested that RPE replacement could be a means to attenuate photoreceptor cell loss. This prompted exploration of the possibility to use pluripotent stem cells (PSCs) as a potential source for "healthy and young" RPE cells for such cell-based therapy of AMD. Various approaches ranging from the use of allogeneic embryonic stem cells to autologous induced pluripotent stem cells are now being tested within early clinical trials. Such PSC-derived RPE cells are either injected into the subretinal space as a suspension, or transplanted as a monolayer patch upon scaffold support. Although most of these approaches are at early clinical stages, safety of the RPE product has been demonstrated by several of these studies. Here, we review the concept of cell-based therapy of AMD and provide an update on current progress in the field of RPE transplantation.
Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats. [2022]Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration. iPSC-RPE cultured as a polarized monolayer on a nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day-old immunodeficient RCS rat pups and evaluated after 1, 4, and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE-specific markers, performed phagocytic function, and contributed to vision preservation. At 11-months post-implantation, RPE survival was observed in only 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11-month time point was associated with peri-membrane fibrosis, immune reaction through the activation of macrophages (CD 68 expression), and the transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.