Determining Whether Leukine May Have Therapeutic Effects in Alzheimer’s Disease

Huntington Potter, Ph.D

University of South Florida College of Medicine

Grant Program:

Clinical Neuroscience Research

Funded in:

April 2011, for 3 years

Funding Amount:


Lay Summary

Determining whether Leukine may have therapeutic effects in Alzheimer’s disease

Investigators will undertake an initial study of the Food and Drug Administration (FDA)-approved drug Leukine in a small number of patients with Alzheimer’s disease, to obtain preliminary evidence of whether the drug shows positive effects on patients’ cognitive abilities and helps to arrest brain atrophy.

Alzheimer’s disease affects between one-third and one-half of all adults over the age of 85, and the few approved drugs for treating cognitive decline in patients produce only minimal effects. No therapies have been shown to prevent the disease or reverse its course of cognitive decline. Investigators at the University of South Florida, however, have developed preliminary data suggesting that the recombinant drug Leukine, approved by the FDA and used for two decades in treating patients with leukemia, might help to reverse the abnormal build-up of brain amyloid in Alzheimer’s disease patients, and correspondingly might improve patients’ cognitive functioning.

Leukine stimulates immune system macrophages, which ingest and dispose of harmful microorganisms and waste products. Based on evidence that patients with the autoimmune disease rheumatoid arthritis do not tend to develop Alzheimer’s disease, the investigators first determined that a factor in these patients called “Granulocyte-Macrophage-CSF (GMCSF)” that stimulates production of immune system macrophages might help to protect them from developing Alzheimer’s. That possibility is consistent with recent research suggesting that patients with Alzheimer’s disease may have reduced capacity to clear away amyloid from the brain. GMCSF is the active ingredient in Leukine.

In prior studies, these researchers gave Leukine to the animal model of Alzheimer’s disease and found that it reduced brain amyloid levels and completely reversed the animals’ cognitive impairment. Then they found promising evidence of Leukine’s effect on cognition in humans by reviewing data from a prior study of cancer patients. Study patients who had received Leukine to enhance bone marrow production of macrophages and other immune cells, following hematopoietic stem cell transplantation had significantly better total neurocognitive performance at six months and one year compared to patients who did not receive Leukine.

Based on the promising animal model studies and on the retrospective study of Leukine’s effects in leukemia patients, the researchers now plan to investigate Leukine’s effects in patients with Alzheimer’s disease in a clinical study that has been approved by the University of South Florida’s Institutional Review Board (IRB). They will study 40 patients with mild-to-moderate Alzheimer’s disease, in which 20 patients will receive Leukine and 20 will receive a placebo. They hypothesize that patients treated with Leukine will show better cognitive functioning and less brain tissue loss than patients receiving placebo.

Patients in both groups will receive baseline MRI imaging to assess amyloid build-up, and neurocognitive performance. Then, the 20 patients that will receive Leukine will be divided into three groups (two groups of five patients each and one group of ten patients) as will the 20 patients that will receive placebo, so that each group (Leukine and placebo) can be tested serially to determine the best dose of Leukine. The first group of five patients on Leukine will receive a three-week course of treatment at a dose that is 50 percent lower than that given to leukemia patients to assess tolerability and brain and cognitive effects, compared to first group of five patients receiving placebo.  If tolerability is not a problem, the second group of Leukine patients will receive the full dose of Leukine over the three-week treatment period and be compared to the second group of placebo patients.

Based on the results using the two different dosages, researchers will determine the best dose to be given to the final group of ten patients receiving Leukine; these patients similarly will be compared to the ten patients receiving placebo.  They will determine whether Leukine patients, in comparison to placebo patients, show better cognitive functioning, less atrophy in the brain’s medial temporal area, improvements in activities of daily living, and reduced levels of Alzheimer’s disease biomarkers in the blood.

Benefits and Challenges: Leukine is not a new drug; it already has met FDA requirements for demonstrating relative safety and efficacy in treating leukemia patients.  One challenge now is to determine that Leukine is tolerable and safe in Alzheimer’s disease patients. The study has been carefully designed to assess this by starting with a low dose and assessing effects before increasing the dose to full strength.   A second challenge is to see whether the three-week course of treatment is sufficient to show any effect on brain amyloid and cognition. If not, additional, longer, studies may be needed.

Significance: This first study in Alzheimer’s disease patients, if successful, would lead to larger-scale studies that could demonstrate that Leukine effectively treats this devastating degenerative disorder.

Investigator Biographies

Huntington Potter, Ph.D

Harvard College AB 1972 Physics & Chemistry

Harvard University MA 1975 Biochem & Mol Biology

Harvard University PhD PhD 1979 Biochem & Mol Biology

1998-present Professor and Eric Pfeiffer Chair for Research on Alzheimer’s Disease,

2005-2010 Director, NIA/NIH designated Florida Alzheimer’s Disease Research Center

1996 American Society for Cell Biology/Glenn Foundation Award for “outstanding research in aging”

2000 Kaul Foundation “Award for Excellence and a gift of $100,000 for outstanding achievements in the field of neurobiology and gerontology.”

2005 Tampa Bay Business Journal – Health Care Heroes Award – Care Innovation & Research

2005 Nominated for the Kyoto Prize for Advanced Technology for the development of the electroporation technique for transfer of DNA into cells; renominated 2009

2005-present Member, Florida Governors’s Alzheimer’s Disease Advisory Council

2007 Work on electroporation featured in Dr. Oliver Smithies Nobel Lecture as essential for the development of knockout mice for which the 2007 Nobel Prize or Medicine or Physiology was awarded

2009 President of the Faculty of the USF College of Medicine