Double Blind Trial of the Safety and Efficacy of GM-CSF Leukine in the Treatment of Alzheiemer’s Disease

Huntington Potter, Ph.D.

University of Colorado, Aurora, CO, Department of Neurology

Grant Program:

Clinical Neuroscience Research

Funded in:

September 2012, for 3 years

Funding Amount:


Lay Summary

Double Blind Trial of the Safety and Efficacy of GM-CSF Leukine in the Treatment of Alzheiemer's Disease

Investigators will undertake the second phase of their clinical study to determine in a small number of people with Alzheimer’s disease whether the drug Leukine shows promise in improving patients’ cognitive abilities and arrests brain atrophy.

About 40 percent of people over the age of 85 have Alzheimer’s disease (AD). No current therapies can arrest or reverse its course, and the few approved AD therapies only minimally slow cognitive decline.  Investigators are exploring the drug Leukine as a potential AD treatment. Leukine currently is approved by the Food and Drug Administration for treating leukemia. The Foundation’s Directors in April 2011 approved support for a clinical study of Leukine, based on observations in several animal and human studies.

Among these observations: 1) Animal model studies conducted by the investigators showed that Leukine reduced the abnormal build-up of brain amyloid that is a hallmark of AD; 2) Analysis of data from a prior controlled trial of Leukine in patients with leukemia found that the drug not only enhanced development of immune system “macrophages,” which clear away debris, but also resulted in significantly better cognitive functioning in the Leukine-treated patients at both six months and a year following treatment; and 3) Patients with autoimmune rheumatoid arthritis do

not tend to develop AD, possibly due to a factor in the patients—called “Granulocyte-Macrophage- CSF (GMCSF)”–that stimulates production of immune macrophages. GMCSF is the active ingredient in Leukine. The common thread, therefore, is that Leukine might stimulate production of macrophages that help to clear way amyloid and prevent it from accumulating in the brain.

The investigators hypothesize that patients treated with Leukine will show better cognitive functioning, reduced amyloid build-up, and less brain tissue loss compared to patients receiving placebo. They have successfully completed the first phase of the double-blind study (in which neither the clinicians nor the patient know what substance the patient is receiving). In this phase, which was conducted at the University of South Florida, investigators enrolled 11 AD patients who were randomly assigned to receive either Leukine, at half of the standard dose, or a placebo. All participants completed the three-week treatment course with no adverse effects. Investigators now will initiate the second Phase of the study in a total of 40 AD patients. This phase will be conducted at the University of Colorado, where the principal investigator recently moved to assume the role of director of the Alzheimer’s disease program. The 40 patients will be randomly assigned (20 patients in each group) to receive Leukine —at the standard full dose—or placebo. Investigators will assess tolerability of the full dose of Leukine treatment. Additionally, they will determine whether the Leukine-treated patients, compared to those receiving placebo, show: 1) better functioning on cognitive tests; 2) less atrophy in the brain’s medial temporal area as determined by brain imaging; 3) reduced levels of AD biomarkers in the blood; and 4) improvement in activities of daily living.

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. Results from the first phase of the study indicate that Leukine, at half the standard dose, is tolerable and safe in AD patients. Now they will confirm that this is also the case for patients receiving full-dose Leukine. Additionally, investigators will have to determine whether a three-week course of Leukine treatment is sufficient to show any effect on the brain and on cognition. If not, this will establish the need for undertaking a longer, and possibly larger, study in AD patients prior to initiating a large-scale clinical trial.

Significance: If promising results are obtained, the research would lead to a larger-scale study of a potentially promising drug treatment for 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