Partner Therapeutics, Inc. (PTx) have published the results of an investigator-initiated trial (NCT01409915) evaluating the safety, tolerability and efficacy of Leukine? (sargramostim, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) in patients with mild-to-moderate Alzheimer’s disease (AD).

The results of the randomised, double-blind, placebo-controlled Phase II trial were published in Alzheimer’s & Dementia: Translational Research and Clinical Interventions.

Professor Huntington Potter from the University of Colorado (CU) Anschutz Medical Campus and an investigator on the trial, commented: “The goal of the clinical trial was to examine the impact of a natural human protein called granulocyte-macrophage colony stimulating factor (GM-CSF) on people living with Alzheimer’s disease. We tested Leukine because people with rheumatoid arthritis tend not to get Alzheimer’s disease and we had previously found GM-CSF, which is increased in the blood of people with rheumatoid arthritis, reduced amyloid deposition in Alzheimer’s mice and returned their poor memory to normal after a few weeks of treatment. Thus, naturally increased levels of GM-CSF in people with rheumatoid arthritis may be one reason that they are protected from Alzheimer’s disease. Human GM-CSF is the active compound in the known human drug Leukine, and we are the first to study its effect on people with Alzheimer’s disease.”

In the trial participants were randomised to receive injections of either Leukine at a dose of 250 mcg/m2/day subcutaneous injection for five days a week for three weeks (n=20) or saline placebo (n=20). All but three study participants were recruited and treated at CU Anschutz , the others were treated at the University of South Florida.

The CU researchers conducted and studied multiple neurological, neuropsychological, cell, cytokine, AD pathology biomarkers and neuroimaging assessments. They found that short term treatment with Leukine:

1. was safe and well-tolerated by participants. The most common Leukine-associated adverse events were dermatological (16 for Leukine versus five for placebo), gastrointestinal (eight versus five) and headache (eight versus two). These side effects were consistent with the Leukine label and there were no serious adverse events related to study drug.

2. showed significant reversal of cognitive loss, as measured by the MMSE (Mini-Mental State Exam): cognitive measures of memory improved by almost two points in the 30 point MMSE compared to baseline; Leukine-treated patients did better than placebo-treated patients after three weeks of treatment and the improvement lasted up to 45 days post treatment;

3. modulated blood-based biomarkers of AD towards normal levels; plasma amyloid marker Abeta40 (decreased in AD) increased 10 percent and plasma markers of neurodegeneration (total Tau and UCH-L1) decreased 24 percent and 42 percent, respectively; and

4.  increased innate and other immune cells and modulated cytokine measures.

“These results suggest that short-term Leukine treatment leads to innate immune system activation, cognition and memory improvement, and partial normalisation of blood measures of amyloid and tau pathology and neuronal damage in participants with mild-to-moderate Alzheimer’s disease,” said Dr Potter. He added: “this surprising finding, that stimulating the innate immune system may be a new treatment approach, induced us to start a larger trial of Leukine in Alzheimer’s disease with more participants treated over a longer time. This new trial will be funded by the Alzheimer’s Association/Part The Cloud, the University of Colorado, the Global Down Syndrome Foundation and by a large grant recently awarded from the National Institute on Aging.”

Leukine is currently not approved for the treatment of Alzheimer’s disease.