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:

  1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeld-Jakob Disease(CJD), Down's syndrome, etc.)
  2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
  3. Seizure disorder
  4. History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, vitamin B12 or folate deficiency, other laboratory values, etc.)
  5. Clinically significant abnormal T4 or TSH

• Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:

  1. Respiratory insufficiency
  2. Bradycardia (<45/min.) or tachycardia (>100/min.)
  3. 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)
  4. 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.