Leukine (sargramostim) is an immune system stimulator that works to boost the number and function of white blood cells and so reduce the risk of infection. Initially developed by Sanofi and later acquired by Partner Therapeutics, it was approved for human use by U.S. Food and Drug Administration (FDA) in 1991.

It is used to treat conditions in which white blood cell counts are low, such as in certain types of leukemia (a blood cancer) or in patients who received a bone marrow transplant.

Leukine is currently being investigated as a potential treatment for cognitive problems related to Alzheimer’s disease.

How Leukine works

Leukine is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF). White blood cells such as granulocytes and macrophages are key components that allow the immune system to fight off infections by attacking and digesting foreign organisms. These cells are produced in the bone marrow (a sponge-like substance that fills the center of some bones in the body) with the help of growth factors such as GM-CSF.

Alzheimer’s disease is marked by abnormal protein deposits called beta-amyloid plaques in the brain that are harmful to nerve cells. GM-CSF is thought to stimulate macrophages in the blood and local brain immune cells (microglia) to “eat” these proteins, and possibly slow or stop disease progression.

The therapy is also reported to have the added benefit of not causing microglial cells to become overactive — a phenomenon that can harm the brain, as excessively stimulated microglia release inflammatory chemicals that are toxic to nerve cells. At the same time, GM-CSF is thought to promote the secretion of other immune-related chemicals that work to protect the brain.

Studies on mice models of Alzheimer’s disease found that 5 µg of GM-CSF injected directly into their brains, or daily under the skin for 20 day, was able to drastically reduce the amount of beta-amyloid protein in the brain and improve the animals’ cognitive abilities.

Leukine in clinical trials

A Phase 2 clinical trial (NCT01409915) is underway in 40 patients with mild-to-moderate Alzheimer’s disease. Patients will receive either Leukine injected under the skin at doses of 250 µg per m2 of body surface daily for five days a week or placebo, with each treatment given for a total of three weeks. The trial aims to determine the safety and tolerability of Leukine, as well as its effects on cognition by monitoring patients for up to three months after treatment ends.

The study began in 2011 and is set to finish in November 2018. Interim data on 32 participants were presented at the Alzheimer’s Association International Conference in 2017. Patients given Leukine increased their mini-mental state examination (MMSE) scores by an average of 1.5 points, while those on placebo experienced no changes, data showed, but no difference between groups was noted in other cognitive tests for Alzheimer’s disease. The ability to carry out activities of daily living (ADL scores) briefly improved after three weeks of treatment with Leukine, but this benefit did not last.

The trial is being conducted by the University of Colorado, with the Byrd Alzheimer’s Institute of the University of Southern Florida. In 2016, it was awarded a two-year $1 million grant by the Alzheimer’s Association to extend this pilot study into a longer trial, one with 24 weeks of treatment and 45 days of follow-up. The status of this extension is not clear.

A separate Phase 2 trial (NCT02667496) examining Leukine and its ability to ease cognitive impairment in Alzheimer’s patients was planned by Sanofi and set to start in 2016. But it was withdrawn from active status due to poor enrollment, the trial document states.


