Origin: The State of RP and The Blessing of Hope

Retinitis Pigmentosa (RP) is a rare genetic disease in which the retina's visual cells gradually degenerate due to genetic abnormalities, leading to progressive visual field constriction and ultimately severe, incurable vision impairment.

To date, no treatment method can radically cure RP. Therapy is limited to symptomatic approaches, such as vitamin A supplements and cataract surgery, which can only marginally delay disease progression. Consequently, many patients and their families live with the anxiety that "the decline in vision cannot be halted."

In recent years, however, reports have begun to emerge indicating that certain treatments can indeed enhance visual function. A beacon of hope has started to illuminate the medical field. For instance, in gene therapy treatments for specific types of RP gene mutations, cases demonstrating improvements in visual field and acuity have started to emerge.

However, RP is a highly heterogeneous disease involving over 260 distinct genes. Therefore, an approach to develop gene-specific treatments has limitations. Against this backdrop, the prospect of stem cell therapy—which aims to "protect the retina itself irrespective of the genetic type involved"—is rapidly gaining traction.

Stem cells offer the potential to repair and regenerate the retina, thereby halting disease progression. This possibility is already manifesting as positive outcomes in some RP patients. The era of resigning oneself to vision loss is transforming into one where vision may be preserved. Stem cell therapy is currently paving the way for this significant change.

Potential Vision Improvement from Stem Cell Therapy—Three Functions Supporting "Retinal Protective Power"

Promoting regeneration of injured retina.

Stem cells possess the ability to differentiate into cells resembling photoreceptor cells or retinal pigment epithelial (RPE) cells under specific conditions. By leveraging this capability, it is anticipated that depleted photoreceptor cells can be replaced, thereby restoring the ability to respond to light.

For example, reports indicate that when stem cells were transplanted into Retinitis Pigmentosa (RP) patients with significant visual impairment, both retinal thickness and electrical responses recovered. Consequently, even if complete vision restoration is not achieved, there is hope that "some visual function may be regained."

Protecting surviving visual cells

Stem cells secrete neurotrophic factors and growth factors within the retina. This consequently supports the function of residual visual cells, facilitating the preservation of existing vision.

This effect is also referred to as the "paracrine effect," where stem cells exert a positive influence on their surroundings. Even if they do not differentiate into new cells, this provides significant benefits to the retina.

Indeed, there have been reports that some patients reported experiencing "a widened field of vision after treatment" or "becoming slightly stronger in darkness."

Suppressing Inflammation and Immune Response that Accelerates Progression

It has become evident that the progression of RP involves not only genetic damage to visual cells, but also chronic inflammatory reactions and immune dysfunction. Stem cells also possess the capacity to suppress these inflammatory and immune-mediated damages.

Anti-inflammatory cytokines secreted by stem cells are believed to calm the retinal environment and reduce damage to retinal cells. This essentially "curbs a dysregulated immune response, calming the retinal environment, thereby allowing retinal cells to focus on recovery."

These three pillars serve as the foundation for addressing RP developments.

The appeal of stem cell therapy is that it is not limited to a singular function, but rather possesses the capability to support the retina through diverse mechanisms.

• For depleted cells: The capacity for new cell generation (regeneration)
• For fatigued cells: The strength to maintain and support (protection).
• For excessive inflammation: The power to soothe and balance (modulation).

Through various collaborative mechanisms, the entire retinal environment is meticulously organized, thereby establishing a foundation for the preservation of vision.

KEY POINTS:

• Stem cells possess the ability to differentiate into visual or RPE cells to aid regeneration.
• It is anticipated to support the preservation of vision by secreting nutritional factors, thereby protecting existing visual cells.
• It is possible to slow the rate of progression by suppressing inflammation and abnormal immune responses.
• The intrinsic value of stem cell therapy lies in its three-pronged approach: regeneration, protection, and inflammation suppression.

Latest Clinical Trials in RP Patients and Results

Enhanced Vision and Visual Field with a Single Administration of Umbilical Cord-Derived MSCs

In a study, umbilical cord-derived stem cells (WJ-MSCs) were transplanted once into the posterior segment of the eye (subtenonally) of RP patients. During 1-year post-treatment follow-up:

• Visual acuity improved, and the number of readable characters increased by over 10 characters (an approximate 2-line improvement in vision testing).
• Retinal thickness was restored, and the light-sensing portion (photoreceptor layer) increased.
• In retinal function tests (electroretinograms), responses also improved.

This increase was observed irrespective of gene type (dominant or recessive), providing reassurance for individuals concerned about the effect's relevance to their specific genetic makeup.

Confirmation of Enhanced Visual Acuity and Safety with Autologous Bone Marrow Stem Cells

At the University of California, Davis, a study was conducted in which autologous stem cells collected from patients' bones were injected into their eyes (7 participants). Results:

• Objective vision improvement was confirmed in 4 out of 7 individuals.
• The field of view is also maintained or partially increased.
• No adverse effects, excellent safety profile.

The congruence between patient-reported experience of 'improved vision' and objective test results holds significant meaning. This represents the moment when 'change' is observed within the relentless progression of Retinitis Pigmentosa (RP).

Developmental Emphasis Confirmed in 3-Year Monitoring

In another study, RP patients who received periodic WJ-MSC administration combined with visual rehabilitation (magnetic stimulation training) were monitored for 3 years. Compared to the untreated group:

• The rate of field of view reduction is significantly slower.
• Retinal function tests (electroretinogram) also indicate a trend towards preservation.
• Average vision remains stable, with many cases showing no deterioration.

The sense of security in the daily lives of RP patients is significantly enhanced merely by halting or slowing the progression of the condition. This trial yielded valuable results, demonstrating that "stem cell therapy has the potential to alter the disease course."

The upward trend in cases represents our greatest hope.

Retinitis Pigmentosa (RP) is a condition in which marked improvement is seldom observed, often leading to the perception that 'any efforts are futile.' However, the finding from this clinical research that certain individuals experienced an improvement in visual function, even if only in a few isolated cases, served as a pivotal moment, restoring confidence that 'further interventions are still possible.'

KEY POINTS:

• A single administration of WJ-MSC demonstrated improvements in vision, visual field, and retinal response.
• Objective visual improvement was confirmed in 4 of 7 individuals treated with autologous bone marrow stem cells, demonstrating a favorable safety profile.
• In a 3-year monitoring study, clear developmental suppression was observed.
• The observation of instances where visual function has improved offers the most significant hope for patients with Retinitis Pigmentosa.

Why are WJ-MSC derived from Wharton's Jelly optimal for RP patients?

Painless Extraction, Cellular Rejuvenation, and Distinct Vitality

WJ-MSC are stem cells derived from the umbilical cords of newborn infants. This tissue is naturally discarded post-delivery, enabling its procurement without imposing any burden on the patient's body.

Additionally, a key characteristic is that these stem cells retain their youthful state from birth.

• Rapid proliferation rate
• Aging is not easy.
• High vitality, with an expectation of sustained therapeutic efficacy.

Even when compared to stem cells derived from bone marrow or adipose tissue, multiple studies demonstrate superior viability in culture and proliferative capacity. This means that, from a smaller amount of starting material, the required number of cells for therapeutic applications can be reliably obtained, indicating that WJ-MSCs achieve an optimal balance between quality and quantity.

Low rejection rate, user-friendly, and safe.

A key concern in stem cell therapy is immune rejection, but WJ-MSC has been demonstrated to carry a very low risk of this.

• Foreign cells can be readily accepted by the body.
• In actual clinical research, there have been reports of no adverse effects for 1 year.
• Stimulating the immune system is challenging, and it even possesses anti-inflammatory actions.

These characteristics indicate that WJ-MSCs offer significant practical advantages for allogeneic therapies (treatments using donor-derived cells). This eliminates the need for time-consuming autologous cell extraction and preparation, as well as associated surgical procedures. Instead, pre-prepared cells can be directly administered when treatment is indicated, which is a major benefit.

Comprising a rich array of components for the protection of visual cells and the optimization of the retinal environment.

WJ-MSCs are highly valued not only for their regenerative capabilities but also for their protective and adaptive functions.

• Neurotrophic factors that protect neurons (BDNF, NGF, etc.) are secreted in large quantities.
• Anti-inflammatory factors (e.g., IL-10, TGF-β, etc.) are also abundant.
• Growth factors involved in blood flow and metabolism (VEGF, HGF, etc.) are also included.

These substances are believed to support compromised visual cells in RP, optimize the overall retinal environment, and help slow disease progression or preserve residual visual function.

Has been utilized in clinical practice, with demonstrable effects.

It has been previously reported that clinical studies utilizing WJ-MSCs have shown several instances of improved vision and visual field. Furthermore, the fact that these donor-derived WJ-MSCs remained safe and effective offers significant reassurance for patients.

Additionally, a unique strength of WJ-MSC is its breadth of application, such as enabling multiple administrations from the same stem cell preparation.

KEY POINTS:

• WJ-MSCs are youthful and highly viable cells, demonstrating superior efficacy in modulating cell populations for therapeutic purposes.
• Low rejection rates, eliminating the need for autologous cell extraction, thereby reducing the overall burden.
• A substance that protects photoreceptor cells and enhances the retinal microenvironment is secreted abundantly.
• Deployed in clinical practice, with safety and efficacy reports available.

Towards Confident Treatment Choices—How the Safety of Stem Cell Therapy is Evaluated

Documentation of 'No Side Effects' Reported in Clinical Research

• In a Turkish WJ-MSC transplantation study (1-year follow-up), it was explicitly reported that no serious adverse events were associated with ocular or systemic health.
• Even in CD34+ stem cell trials conducted by the University of California, Davis, no infections or complications have been reported.
• Mild eye redness or temporary discomfort was observed in some patients; however, all cases resolved spontaneously within 24 hours without any long-term effects.

These trials are all formal clinical studies conducted on actual RP patients, and the practical results have demonstrably overcome the perception that stem cell therapy is dangerous.

Why is it safe? The reason lies in the cellular properties and the method of administration.

Because of biocompatible cells

Stem cells, particularly WJ-MSCs, are inherently characterized by low immunogenicity.

Even with allogeneic cells, the body does not readily exhibit rejection responses, making them safe cells with a low risk of adverse effects. Furthermore, WJ-MSCs are young and highly vital, and the risk of mutation and malignant transformation is also very low in most cases.

As the delivery method has been proven.

The technique employed (cell administration method) is also a critical element influencing safety. In stem cell therapy, the following practical methods are utilized:

• Intravitreal injection (injection in the eye):A standard technique also used in age-related macular degeneration
• Pemberian di bawah tenon (pemberian di bawah membran sisi luar bola mata):A gentle approach allows without directly touching the retina.

Both are established and widely employed methods in ophthalmology, and to date, no serious complications have been reported.

Key Points

• In a clinical study involving patient RP who received stem cell therapy, no serious adverse events were reported.
• WJ-MSC exhibits low immunogenicity, and the risk of rejection and malignancy is very low.
• Intravitreal injection or sub-Tenon's administration techniques, which have demonstrated safety, are employed for administration.

Conclusion: Transcending the Era Without Treatment—Bringing Hope to RP Patients

Stem cell therapy holds considerable promise for RP, particularly where vision loss is inevitable.

Advanced Retinitis Pigmentosa (RP) has long been considered an untreatable disease. Restoring vision is challenging, and methods to halt its progression have been limited. However, with the advent of stem cell therapy, that fundamental assumption has significantly changed.

Clinical trials have demonstrated improvements in visual acuity and field of vision, alongside the suppression of disease progression. This marks the beginning of an era where it is now possible to optimistically consider that vision may be preserved.

It is effective across a diverse range of RP types, not limited to specific genetic variants, and no serious adverse events have been reported. The definite expansion of treatment options represents the greatest hope for RP patients.

Do not rush; appreciate the optimal care currently available and trust in medical advancements. The era where vision loss no longer needs to be accepted has arrived.