Therapeutic evaluation of low-dose IL-2-based immunomodulatory approach in patients with early Alzeihmer Disease

Prior treatment

• Patients who are likely to require corticosteroids
• Known or supposed history (< or = 5 years) of severe alcoholism or misuse of drugs

Other illness

• Subject with a psychiatric evolutionary and/or badly checked
• History within the past 5 years of a primary or recurrent malignant disease (with the exception of fully excised non-melanoma skin cancers).
• Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders (FTD, LBD, VaD, HD, PD, PSP-CBD)
• Chronic hepatic diseases as indicated by liver function tests abnormalities
• Clinically significant evidence of Active viral infection (CMV, EBV, HCV, HBV, TPHA-VDRL, HIV)
• Current- or medical history of severe cardiopathy

Lab values

• Renal dysfunction at inclusion, clearance <30 mL/min
• Patients with White Blood Count (WBC) < 4.000/mm3; platelets < 100.000/mm3; hematocrit (HCT) < 30%
• Patients with serum bilirubin and creatinine outside normal range

Other

• Abnormal thyroid function
• Therapeutic trial within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid
• Severe dysfunction in a vital organ
• Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
• Patients with organ allografts
• Epileptic subjects
• Subject under guardianship or curatorship
• Subject presenting contraindications to the MRI
• Vascular, inflammatory or expansive, visible lesion in the MRI, which can interfere on the criteria of diagnosis.
• No health insurance
• Women of childbearing potential: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause

• Patients aged > 18
• Clinical and biological diagnosis of AD based on o Progressive amnestic syndrome associated or not with other cognitive impairments o Biological criteria: CSF biomarkers suggestive of AD.
• Brain MRI congruent with the diagnosis, left to the appreciation of the investigator
• CDR (Clinical Dementia Rating Scale) = 0.5 or 1
• If patients have an antidepressant or acetylcholinesterase inhibitors treatment, patients must be treated with stable doses of treatment for at least 1 month before inclusion.
• The subject lives with (or has regular periods of contact with) a permanent caregiver who is ready to attend the inclusion and the clinical follow-up visits (V1, V20, V21, V22), is ready to attend or to be contacted for each treatment visit (V3 to V19), supervises the subject’s compliance with the procedures specified in the protocol, and reports on subject’s condition.
• Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator.
• Have given written informed consent approved by the ethical review board (ERB) governing the site
• The patient has to have a French social security number and be fluent and literate in French.