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

A medicine that is FDA-approved for bone marrow stimulation (called Leukine) will be tested for its ability to be tolerated by Alzheimer's disease patients and potentially to improve their memory.

Preliminary preclinical results demonstrated that GM-CSF (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, we 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, we 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.

• Drug: Sagramostim
  5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
  Other Names:

  • Leukine
  • Granulocyte-Macrophage Colony-Stimulating Factor
• Drug: Saline -- placebo comparator
  subcutaneous injection
  Other Name: Sterile solution of sodium chloride in water

• Experimental: Sagramostim (Leukine)
  5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
  Intervention: Drug: Sagramostim
• Placebo Comparator: Control Group
  Saline -- placebo comparator. Given as a subcutaneous injection.
  Intervention: Drug: Saline -- placebo comparator

Inclusion Criteria:

1. age 55 to 85 years;
2. should have a mild-to-moderate Alzheimer's Disease diagnosis (Mini-Mental State Examination 10-26 inclusive);
3. if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
4. stable on all other medications for at least 30 days prior to screen;
5. should be fluent in English;
6. should be physically able to participate by medical history, clinical exam and tests;
7. should have a study partner to accompany them to scheduled visits.

Exclusion Criteria:

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