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:

1. age 55 to 85 years;

2. should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);

3. 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.

4. if on anti-dementia treatment should be on stable treatment for at least 2 months
(i.e. cholinesterase inhibitor and/or Memantine or Axona);

5. stable on all other medications for at least 30 days prior to screen;

6. should be fluent in English;

7. should be physically able to participate by medical history, clinical exam and tests;

8. 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, or any women who feel they are likely to become pregnant during the
study;

14. prisoners.