Management of Retinitis Pigmentosa Via Combination of Wharton's Jelly-derived Mesenchymal Stem Cells and Magnovision

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-01

Study Completion Date

2022-12-31

Brief Summary

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Purpose To investigate whether the natural progression rate of retinitis pigmentosa (RP) can be decreased with subtenon umbilical cord Wharton's jelly derived mesenchymal stemcell (WJ-MSC) application alone or combination with retinal electromagnetic stimulation (rEMS).

Material and methods The study included prospective analysis of 130 eyes of 80 retinitis pigmentosa patients with a 36-month follow-up duration. Patients constitute 4 groups with similar demographic characteristics. The subtenon WJ-MSC only group consisted of 34 eyes of 32 RP patients as Group1; The rEMS only group consisted of 32 eyes of 16 RP patients as Group2; The combined management group consisted of 32 eyes of 16 RP patients who received combined WJ-MSC and rEMS as Group3; The natural course (control) group consisted of 32 eyes of 16 RP patients who did not receive any treatment were classified as Group4. Fundus autofluorescence surface area (FAF-field), horizontal and vertical ellipsoid zone width (EZW), fundus perimetry deviation index (FPDI), full field electroretinography magnitude (ERG-m) and best corrected visual acuity (BCVA) changes were compared within and between groups after 36 month follow up period.

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Detailed Description

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Retinitis Pigmentosa (RP) is one of the most common inherited diseases of retinopathies. It is estimated to affect 1 in 3000 to 1 in 4000 people globally. Retinitis pigmentosa (RP) is a genetic disease group characterized by progressive loss of photoreceptors. At least 90 different structural and functional proteins have been identified in the sensory retina, which is necessary for the healthy functioning of the visual cycle. At least 300 genes encode these proteins, and their fragments have been identified in the sensory retina. Mutations in any of these 300 genes lead to outer retinal degeneration and RP. In classical RP, genetic mutations primarily impair the functions of rod cells. Structural and functional protein deficiency causes rod cells to enter the dormant phase and undergo apoptosis. The inheritance pattern can be autosomal dominant, autosomal recessive, X-linked, mitochondrial, or spontaneous mutations. The rate of disease progression is different in each inheritance pattern. Patients first complain of difficulty seeing at night and prolonged dark adaptation. As rod cell loss increases, the peripheral visual field begins to narrow. The narrowing of the visual field progresses at a rate of 5-15% each year, depending on the inheritance pattern, and finally, the cone cells are affected. Apoptosis of rod/cone cells results in end-stage RP, then progress to total blindness.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have a high paracrine effect and secrete exosomes containing different growth factors (GFs) and neurotrophins. These peptides in the exosome content are functional and structural peptides for neurons. Peptides that cannot be encoded in RP can be substituted by WJ-MSCs exosomes. Growth factors and neurotrophins in the exosome can accelerate the entry of glucose into retina pigment epithelium (RPE) and photoreceptors and their conversion to ATP, an energy molecule. These neurotrophins can also provide homeostasis, preventing apoptosis by accelerating the phagocytosis of cellular metabolic wastes.

High-frequency repetitive electromagnetic stimulation (rEMS) can modulate ion channels in neurons depending on frequency, magnetic field, and duration variables. If the dormant phase - which is the sleep mode caused by genetic mutations in the sensory retina - is prolonged, apoptosis and permanent photoreceptor loss occur. Activation of ion channels and acceleration of neuromodulation by electromagnetic stimulation can prevent neuronal apoptosis. Scientific studies have also shown that rEMS increases mesenchymal stem cells' exosome degranulation. Another effect of rEMS is the iontophoresis effect. The passage of large molecules into the cells through the scleral pores is possible by changing the electrical charges between neurotrophins and their receptors and increasing the affinity. It can also induce the delivery of higher amounts of GFs and neurotrophins into the subretinal environment and retina.

This prospective clinical study aims to investigate whether RP progression can be slowed or maintained with the inoculation of WJ-MSCs alone into the deep subtenon space or in conjunction with rEMS application compared to the natural course of the disease.

Conditions

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Retinitis Pigmentosa

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

A total of 130 eyes of 80 RP patients who could be checked regularly, mean 36 months of the follow-up period, were included in this study. Four different groups with similar demographic characteristics were created in the cohort

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Only WJ-MSCs

Consisted of 34 eyes of 32 RP patients treated with only WJ-MSCs, and it was applied only once following necessary preparations. After the inoculation of stem cells, the patients were followed up regularly on the 10th day, 3rd month, and every 6 months after that until 36 th months. For ethical reasons, the worse eye was selected to inject the stem cells instead of both eyes.

Group Type ACTIVE_COMPARATOR

Wharton's jelly derived mesenchymal stemcells

Intervention Type BIOLOGICAL

The WJ-MSCs suspension from the culture was delivered to the operating room by cold chain and used within 24 h. A total of 1.5 ml of the WJ-MSC suspension was immediately injected into the deep subtenon space of each eye.

Only rEMS

Consisted of 32 eyes of 16 RP patients treated with only rEMS. rEMS was applied with a custom-designed helmet once a week for 30 min for 36 months. Both eyes are stimulated at the same time with the specially designed system for ophthalmologic use (MagnoVisionTM).

Group Type ACTIVE_COMPARATOR

Magnovision

Intervention Type DEVICE

Specifically designed helmets producing high-frequency repetitive electromagnetic stimulation (MagnovisionTM, Bioretina Biotechnology, Ankara, Türkiye) stimulated the retinas and visual pathways in both eyes.

WJ-MSCs and rEMS combination

Consisted of 32 eyes of 16 RP patients treated with the WJ-MSCs and rEMS combination. WJ-MSCs were applied first into the deep subtenon space of both eyes after necessary preparations. rEMS application was started 10 days after the WJ-MSC application with a custom-designed helmet for 30 min. WJ-MSCs were inoculated only once, and rEMS was applied regularly once a week for 30 min for 36 months. Both eyes are stimulated at the same time with the specially designed system for ophthalmologic use (MagnoVisionTM).

Group Type ACTIVE_COMPARATOR

Wharton's jelly derived mesenchymal stemcells

Intervention Type BIOLOGICAL

The WJ-MSCs suspension from the culture was delivered to the operating room by cold chain and used within 24 h. A total of 1.5 ml of the WJ-MSC suspension was immediately injected into the deep subtenon space of each eye.

Magnovision

Intervention Type DEVICE

Specifically designed helmets producing high-frequency repetitive electromagnetic stimulation (MagnovisionTM, Bioretina Biotechnology, Ankara, Türkiye) stimulated the retinas and visual pathways in both eyes.

The natural course

The natural course (control) group consisted of 32 eyes of 16 RP patients who received no treatment and were regularly followed until the 36th month. This group comprised patients who did not accept any treatment and/or were in good condition at baseline.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Wharton's jelly derived mesenchymal stemcells

The WJ-MSCs suspension from the culture was delivered to the operating room by cold chain and used within 24 h. A total of 1.5 ml of the WJ-MSC suspension was immediately injected into the deep subtenon space of each eye.

Intervention Type BIOLOGICAL

Magnovision

Specifically designed helmets producing high-frequency repetitive electromagnetic stimulation (MagnovisionTM, Bioretina Biotechnology, Ankara, Türkiye) stimulated the retinas and visual pathways in both eyes.

Intervention Type DEVICE

Other Intervention Names

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Electromagnetic stimulator iontophoresis neuromodulator

Eligibility Criteria

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Inclusion Criteria

* RP patients of any genotype and phenotype;
* BCVA better than 35 letters;
* Any degree and kind of visual field loss;
* Over 18 years old.

Exclusion Criteria

* The presence of glaucoma,
* Dense cataracts
* Dense vitreus opacities
* Autoimmune retinopathy-like clinical picture
* Any degree of smoking
* Presence of systemic neurological disease with seizure
* Presence of a cardiac pacemaker.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No