Researchers at the University of South Florida and James A. Haley Hospital have found that a human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment. The findings were revealed after conducting experiments on mice genetically altered to develop Alzheimer's disease.
Writing about their work in the journal Neuroscience, the researchers revealed that the granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer's mice, increased the production of new neurons, and promoted nerve cell connections.
AdvertisementAccording to background information in the research article, GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation.
The report points out that GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection, and that it is used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants.
Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.
"GCSF has been used and studied clinically for a long time, but we're the first group to apply it to Alzheimer's disease. This growth factor could potentially provide a powerful new therapy for Alzheimer's disease - one that may actually reverse disease, not just alleviate symptoms like currently available drugs," said USF neuroscientist Dr. Juan Sanchez-Ramos, the study's lead author.
The study on mice showed that injections under the skin of filgrastim (Neupogen) - one of three commercially available GCSF compounds - mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behaviour in the Alzheimer's mice.
"The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain," Dr. Sanchez-Ramos said.
The promising findings in 52 elderly mice, equivalent to the human ages of 60 to 80 years, have prompted the Alzheimer's Drug Discovery Foundation to fund a pilot clinical trial at USF's Byrd Alzheimer's Center.
The randomised, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer's disease.
"The concept of using GCSF to harness bone marrow-derived cells for Alzheimer's therapy is exciting and the findings in mice are promising, but we still need to prove that this works in humans," said Dr. Raj, a physician researcher at the Byrd Alzheimer's Center at USF Health.