Clinical Study of Regulatory T Cells (Tregs) in the Treatment of Neurodegenerative Diseases

Prior treatment

• Clinically significant cardiology, defined as: myocardial infarction, NYHA-graded class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia, or ECG evidence of acute ischemia or abnormal conduction system within 6 months prior to enrollment;
• Treatment with another investigational drug, biologic, or device within 30 days or 5 half-lives (whichever is longer) of the screening period. Patient participation in observational/non-interventional clinical studies will be discussed with the Medical Monitor;
• Prior treatment with ALS gene or cell therapy;
• Current use of antipsychotics, antiepileptic drugs (except benzodiazepines, gabapentin, pre-Bahrain) or class 1 (e.g., flecainide) or class 3 (e.g., amiodarone) antiarrhythmic drugs;

Other illness

• uncontrolled infection;
• \< 3 drugs do not adequately control hypertension;
• Documented history of pulmonary embolism within 6 months of enrollment;
• Patients with a history of coronary artery bypass grafting or angioplasty will be evaluated by cardiology and considered on a case-by-case basis;
• Seropositive for HIV, hepatitis B or hepatitis C;
• History of clinically significant tumor, liver or kidney disease, or other uncontrolled disease;
• Other conditions that the investigator considers unsuitable for enrollment.

Other

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• Subjects with any of the following cannot be enrolled in this study:
• Pregnant or lactating patients;
• Patients of childbearing potential or males with partners of childbearing potential who are unwilling to use contraception;
• Participation in any other interventional study;
• presence of a feeding tube;
• Subjects who, in the opinion of the investigator, are at significant risk of suicide;

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• Patients must meet all of the following criteria to be eligible for enrollment in this study:
• Male or female patients aged 18 to 70 years;
• According to current international diagnostic criteria:
  • ALS: defined by the Gold Coast Diagnostic Criteria (Shefner, 2020) as having a diagnosis of sporadic or familial amyotrophic lateral sclerosis (ALS), diagnosed as a probable, probable, or definite patient with laboratory support according to the World Federation of Neurology El Escorial criteria;
• If there is a stable dose for more than one month prior to study entry. For example, patients with ALS can continue treatment with riluzole (Rilutek®) and/or edaravone (Radicava®);
• Patients must have \> two weeks after the end of major surgery and after the completion of participation in other research trials;
• Patients must have recovered from clinical toxicity (CTCAE \[5th Edition\] toxicity values have resolved to \< 2);
• Serum creatinine less than or equal to 2.0 mg/dL;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal;
• Bilirubin \< 1.5 (except Gilbert's disease);
• Lung slow vital capacity (SVC) \> 70% of predicted normal;
• No history of abnormal bleeding tendency;
• Informed consent must be obtained prior to performing any study-related procedures that are not part of standard medical care, with the understanding that the participant may withdraw from the study without influence for the future medical care.