low dose il-2 in the treatment of immune-associated als syndrome

Conditions: Amyotrophic Lateral Sclerosis

Summary: the purpose of this study was to evaluate the efficacy and safety of low-dose il-2 in the treatment of immunorelated als syndrome.

this is a single-center, open-label, self-controlled clinical study with a sample size of 10 patients for 48 weeks, including 24 weeks of administration, and 24 weeks of follow-up. during the administration period, medication was given for 2 weeks and rest for 2 weeks, as a course of treatment, with a total of 6 courses for 24 weeks. during the administration period, the drug was given on alternate days, and il-2 1miu was subcutaneously injected the next day for 7 times, and then rested for 2 weeks, and the cycle was repeated for 6 times. the primary outcome index was the change in the rate of alsfrs-r score between administration period and follow-up period. secondary outcome measures included changes in the rate of alsaq-40 score, roads score, mrc score, survival time, fvc%, treg and cd4+ t cell subsets, inflammatory factors, serum and cerebrospinal fluid nfl during follow-up versus administration , changes in the inhibition function of treg; exploratory outcome indicators included the change degree of compound muscle action potential (cmap) amplitude, quantitative analysis of corneal nerve morphologic changes by corneal confocal microscopy (ccm), treg single-cell sequencing transcriptome analysis. the related safety indexes were also evaluated.

Eligibility criteria:
inclusion criteria: * 18-70 years old; * clinically diagnosed with als syndrome, i.e., with als -like manifestations, consisting of a combination of upper and/or lower motor neuron damage; * significant abnormalities with rheumatoid immune-related indicators, or diagnoses of immune-mediated als syndrome, including but not limited to multifocal motor neuropathy (mmn), lewis-sumner syndrome, and other als-like syndromes with an immune background that cannot be clearly classified; * poor treatment with conventional hormones or gamma globulin; * permitted concomitant treatment: oral prednisone or equivalent doses of other glucocorticoids (≤1.0mg/kg/d); oral routine dose of immunosuppressants or immunomodulators, such as cyclophosphamide, tacrolimus, etc.; routine oral doses such as too much force; doses and types of accompanying therapeutic drugs should not be changed from the trial enrollment to the end of follow-up. * for women of reproductive age, contraception for at least 2 weeks at the time of enrolment and negative urine hcg; * reasonable and effective contraceptive measures should be taken by subjects of childbearing age from the time of trial enrollment to the end of follow-up; * signed informed consent. exclusion criteria: * allergic or intolerance to il2; * receive non-standard treatment or use of excessive dose of glucocorticoids or gamma globulin intravenously within 2 months before enrollment; * vaccination within 6 months before enrolment or between enrolment and the end of follow-up; * peripheral venous white blood cells \< 2000/mm3, lymphocytes \< 600/mm3, platelets \< 80,000 /mm3; * complicated with severe infection or inflammation, such as bacteremia, sepsis, etc.; * complicated blood system diseases, infectious diseases (hepatitis, hiv, tuberculosis, etc.), mental diseases, dementia, severe hypotension, substance abuse history, malignant tumor history, organ transplantation history, etc.; * severe liver, kidney, lung or heart dysfunction: heart failure (≥nyha grade iii), renal insufficiency (creatinine clearance ≤30ml/min), abnormal liver function (3 times the upper limit of normal \>); * pregnant and lactating women; * currently participating in other clinical studies or using other investigational drugs.