Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease

Preliminary preclinical results demonstrated that GM-CSF (Granulocyte macrophage colony-stimulating factor, e.g. Leukine®/Sargramostim) rapidly reduced cerebral amyloid deposition and completely reversed memory deficits in transgenic mouse models of Alzheimer's Disease (AD). To assess the efficacy of GM-CSF in humans, the investigators performed a retrospective analysis of a cognition study of human patients undergoing hematopoietic cell transplantation for cancer and who garner cognitive impairments from the chemotherapy or irradiation. In the patients that received a colony-stimulating factor (CSF) to stimulate the bone marrow and recover immune system function, the investigators found that those who received GM-CSF (Leukine®/Sargramostim) plus G-CSF (Filigrastim) significantly improved in cognitive function as compared to those who received G-CSF alone. These findings combined with over two decades of accrued safety data using recombinant human GM-CSF, Leukine®/Sargramostim, in elderly leukopenic patients, suggested that Leukine® should be tested as a treatment to reverse cerebral amyloid pathology and cognitive impairment in AD.

Inclusion criteria

• age 55 to 85 years;
• should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);
• should have evidence of elevated cortical amyloid by PET using florbetapir F18 (Amyvid) [i.e. a positive scan], assessed qualitatively according to the Amyvid product label.
• if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
• stable on all other medications for at least 30 days prior to screen;
• should be fluent in English;
• should be physically able to participate by medical history, clinical exam and tests;
• should have a study partner to accompany them to scheduled visits.

Exclusion criteria

• clinically relevant arrhythmias;
• a resting pulse less than 50;
• active cancer other than non-melanoma skin cancers;
• use of another investigatory drug within 2 months of screening;
• significant stroke or head trauma by history or MRI;
• contraindication for having a MRI;
• diagnostic and Statistical Manual of Mental Disorders-IV criteria for a current major psychiatric disorder;
• sensitivity to yeast or yeast products;
• impaired kidney function as measured by a Glomerular Filtration Rate less than 60 milliliters/min;
• preexisting fluid retention, pulmonary infiltrates, or congestive heart failure;
• history of moderate-to-severe lung disease;
• history of moderate-to-severe liver disease;
• pregnant women, or any women who feel they are likely to become pregnant during the study;
• prisoners.