About Treg Therapy
A Detailed Overview of Treg-Based Immune Regenerative Medicine
Recent advances have significantly improved our understanding of the pathophysiology of amyotrophic lateral sclerosis (ALS), highlighting that suppressing persistent neuroinflammation is a key factor in slowing disease progression.
At our clinic, we aim to stabilize disease progression by restoring the cells that regulate excessive immune responses.
About Treg Therapy
About Treg Therapy
Chronic Neuroinflammation and Immune Dysregulation
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which genetic, environmental, and age-related factors contribute to a breakdown in neural and immune homeostasis, leading to persistent neuroinflammation and the gradual degeneration and loss of motor neurons. A key therapeutic challenge is controlling neuroinflammation, in which the immune system—normally responsible for protection—becomes dysregulated and contributes to damage of motor neurons.
In patients with ALS, excessive activation of microglia in the brain and dysregulation of immune responses in peripheral blood have been observed. In particular, a decline in the function of regulatory T cells (Tregs), which play a key role in suppressing inflammation, has been reported to closely correlate with the rate of disease progression.
Mechanism for Restoring Immune Homeostasis
Regulatory T cells (Tregs) are a specialized subset of lymphocytes that act as an “immune brake,” helping to regulate immune responses and prevent excessive immune activation. In patients with ALS, this regulatory function is often impaired. The primary goal of Treg therapy is to restore this lost regulatory capacity by replenishing Treg function and re-establishing immune homeostasis.
In this therapy, cells are collected from the patient’s blood, isolated, and cultured for approximately two months. During this process, dysfunctional Treg cells are restored and expanded ex vivo before being reinfused into the patient. The goal is to strengthen immune regulation and help slow disease progression. As an autologous cell therapy, it carries a low risk of rejection and a reduced risk of infectious complications.
Uniqueness
Key Features and Uniqueness of the Therapy
The World’s First Triple-Combination Therapy
The key feature of this therapy is its three-agent combination approach. In addition to Treg cell supplementation, it includes low-dose IL-2 and CTLA4-Ig. Unlike conventional immunosuppressants, which broadly suppress the immune system, this approach selectively targets excessive immune responses while preserving normal immune function. The goal is to provide a safer and more fundamental therapeutic effect.
Regulatory T Cells (Tregs)
These cells are collected from the patient and expanded in a sterile environment while maintaining their functional integrity. They are intended to restore diminished immune regulatory ("brake") function.
Low-dose interleukin-2(IL-2)
It selectively expands the reinfused Tregs in vivo and further enhances their functional activity. In clinical trials, it has also demonstrated a favorable safety profile, along with suppression of relevant biomarkers.
CTLA4-Ig
It is used in combination to prevent excessive cellular activation that can disrupt immune balance. Like IL-2, it has also been shown to suppress disease-related biomarkers in ALS.
Treatment Flow & Schedule
Treatment Process and Schedule
From Pre-Treatment Evaluation to Follow-Up Care
01Determining Treatment Eligibility
Through blood tests and a medical examination, the physician evaluates factors such as allergies and pre-existing conditions and performs a comprehensive assessment of the patient’s suitability for treatment.
※ Note: The treatment may not be available for all patients, depending on their medical condition.
02Cell Collection
More than three months before infusion, peripheral blood is collected from a vein in the patient’s arm. It serves as the starting material for cells processed into a personalized therapeutic product.
03Isolation and Culture
The cells are expanded over approximately two months in a dedicated facility, and only those that meet strict quality control standards are used for administration.
04Intravenous Administration
The eight administrations are divided into two phases: an initial phase and a maintenance phase.
05 Regular Follow-Up Care
To ensure the safety and efficacy of this treatment, patients are required to return for follow-up visits at 1, 3, and 6 months after completing treatment. During these visits, the physician closely monitors their progress.
※ Note: If hospital visits are difficult due to the patient’s condition, telemedicine consultations may be offered as an alternative.
Treg Therapy: Overview and Treatment Schedule
Five Consecutive Days of Treatment per Cycle
Important Notes Regarding the Treatment Schedule
To ensure stable therapeutic effects of the medication used in this treatment, patients are required to attend the clinic and receive administration for five consecutive days at the start of each treatment cycle (Days 1–5).
As daily visits to the clinic are required, patients are advised to plan their schedule in advance.
- Initial Phase
(Weeks 1–7) - To promote stabilization of the condition, four treatment cycles are administered. Each cycle consists of five consecutive days of treatment, with two-week intervals between cycles.
- Maintenance Phase
(Weeks 9–21) - To maintain and consolidate a favorable clinical condition, a total of four treatment cycles are administered. Each cycle consists of five consecutive days of treatment, with four-week intervals between cycles.
※ Safety-Based Treatment Interruption and Resumption Guidelines
In patients classified as AE3 or higher according to the ALS severity (AE) scale, treatment may be postponed or discontinued at the physician’s discretion. Treatment may be resumed once the patient improves to AE2 or lower and the physician determines it is appropriate to proceed.
Fees & Terms
Fees and Contract Terms
Domestic and International Pricing and Deposit System
This treatment is not covered by public health insurance and is provided as a private medical service. All costs are the responsibility of the patient.
- Patients Residing in Japan
- Per treatment session: JPY 2,000,000 (excluding tax) / Total for 8 sessions: JPY 16,000,000 (excluding tax).
- Patients Residing Outside Japan
- To avoid currency fluctuations, a fixed fee of USD 25,000 (excluding tax) is applied per treatment session.
- Deposit (Refundable Deposit)
- Please transfer JPY 2,000,000 (USD 25,000 for patients residing outside Japan) no later than two weeks prior to the scheduled date of initial blood collection. The reservation will be confirmed upon receipt of payment.
※ Note : The deposit will be credited toward the cost of the final treatment session (Session 8).
※ Note: Initial consultation fees, follow-up consultation fees, and examination fees are charged separately.
※ Note: The treatment fee remains unchanged, even if the dosage of IL-2 or CTLA4-Ig is reduced based on the patient's condition.
Cancellation and Refund Policy
If a patient cancels the treatment for personal reasons within two weeks of the scheduled blood collection date, the deposit already paid will be retained as a cancellation fee and is non-refundable.
However, in cases such as sudden deterioration in the patient’s condition, the patient’s death, or the inability to culture cells due to technical reasons, a refund may be issued after deducting any actual costs incurred. These may include, but are not limited to, testing fees, cell processing costs, material expenses, and personnel costs. Any refund will be limited to the remaining balance, if applicable, and will be calculated on a case-by-case basis according to the stage of treatment at the time of cancellation.
If the standard treatment protocol (IL-2/Rapamycin method) does not produce a sufficient clinical response, the physician may, at their discretion, recommend a change in the cell culture protocol to the IL-7/IL-15 method. The fee for the IL-7/IL-15 method is JPY 2,500,000 per administration. For patients residing outside Japan, the fee is USD 30,000 per treatment. All prices are exclusive of tax.
Treatment Fees and Payment Information
Safety & Patient Rights
Safety and Patients’ Legal Rights
Management of Adverse Events and Support System
"Pain or bruising associated with blood collection, as well as allergic reactions related to intravenous infusion (including fever, chills, nausea, vomiting, hypotension, and anaphylaxis-like symptoms), cannot be completely ruled out. In the unlikely event of any adverse effects, appropriate medical treatment will be provided promptly. Such cases are covered under physician liability insurance and other applicable insurance policies.
This treatment is provided in accordance with a treatment plan submitted to the Minister of Health, Labour and Welfare (Regenerative Medicine Provision Plan No. PC3250265) and following review by a certified special committee on regenerative medicine and related therapies."
Withdrawal of Consent and Information Protection
"The patient’s autonomy in decision-making is fully respected. Patients may choose not to provide consent after receiving an explanation or may withdraw consent at any time after it has been given, without any disadvantage to their future medical care.
In the event of withdrawal of consent, a “Consent Withdrawal Form” must be submitted at the reception."
Patient personal information will be strictly managed in anonymized form and will not be used for any purpose other than this treatment, nor disclosed to any third party without prior authorization. Blood and cell samples collected will be stored under appropriate conditions and properly disposed of after the designated storage period has expired.
