Interleukine-2 (IL-2) Plus Semaglutide in Alzheimer's Disease

Inclusion criteria

• Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria13.
• Male or female age 50 to 86 years
• MMSE between 16-26
• Albumin greater than or equal to 3.0mg/dL
• White Blood Count (WBC) >3,500/mm3; platelets >100,000/mm3; hematocrit (HCT) >32%.
• INR<1.4
• If on medications affecting cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 4 weeks prior to screening and should remain at a stable dosage during the course of the study.
• English language speaking
• Formal education of eight or more years
• Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening
• A family member or caretaker who is expected to be consistently available, administer study drugs of IL-2 and attend study visits throughout the study.
• For AD patients with limited decision-making capacity, the legally authorized representative (LAR) should be present and consent based on the patient's best interest.

Exclusion criteria

• Any untreated bacterial, fungal or viral infection
• Renal dysfunction indicated by serum creatinine greater than 1.5 mg/dL
• Hepatic impairment indicated by Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) greater than two times normal
• Clinically significant pulmonary dysfunction, including a history of chronic pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD]) associated with functional limitation, or FEV₁ < 75% of predicted for age and height when pulmonary function testing indicated to evaluate ongoing respiratory symptoms
• Clinically significant cardiac dysfunction, including a history of uncontrolled cardiac arrhythmias, prior cardiac tamponade, or unstable angina or myocardial infarction within 3 months prior to screening, or clinically significant abnormalities on baseline electrocardiogram (ECG). LVEF< 40% in echocardiography if clinically indicated based on ongoing cardiac symptoms or abnormal ECG findings
• Hypersensitivity or allergy to IL-2
• History of severe gastrointestinal disease Hospitalization or change of chronic concomitant medication within one month prior to screening.
• History of hemorrhage or infarct or > 3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor with the exception of small incidental meningiomas) in prior CT or MRI.
• Clinical or laboratory findings consistent with:

• Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeld-Jakob Disease(CJD), Down's syndrome, etc.)
• Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
• Seizure disorder
• History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, vitamin B12 or folate deficiency, other laboratory values, etc.)
• Clinically significant abnormal T4 or TSH
• Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:

• Respiratory insufficiency
• Bradycardia (<45/min.) or tachycardia (>100/min.)
• Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg)
• Uncontrolled diabetes defined by HbA1c >8%
• History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
• History of organ allografts
• Current treatment with insulin or insulin secretagogues (including sulfonylureas or meglitinides)
• Prior GLP-1 RA administration or natural GLP1 supplements intake within the past 6 months
• Disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.).
• Within 4 weeks of screening visit or during the course of the study, concurrent treatment with antipsychotic agents (except risperidone ≤1.5 mg/day, quetiapine ≤100 mg/day, olanzapine ≤5 mg/day, and aripiprazole ≤10 mg/day), antiepileptics (except lamotrigine, gabapentin and pregabalin for nonseizure indications), centrally active anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.), opiate analgesics, systemic corticosteroids, psychostimulants, antiparkinsonian medications (except for non-parkinsonian indications) and mood stabilizers (e.g., valproate, lithium), sedatives, and anxiolytics with the exception that use of short- to medium-acting benzodiazepines for treatment of insomnia is permitted, however, use of sedatives or hypnotics should be avoided for 8 hours before administration of cognitive tests.
• Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
• Use of concomitant CYP-metabolized medications with a narrow therapeutic index including warfarin, calcineurin inhibitors, or theophylline)
• Suspected or known drug or alcohol abuse, i.e., more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) indicated by elevated MCV significantly above normal value at screening
• Suspected or known allergy to any components of the study treatments.
• Intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
• Contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; INR >1.4 or other coagulopathy; platelet count of <100,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant medication within 90 days of screening (Note: low dose aspirin is permitted); suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
• Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion.