You are hereMarch 9, 2016
Protein-revved stem cell could transform Alzheimer's treatment
Durham, NC – A new type of engineered stem cell could transform how Alzheimer's disease (AD) is treated and perhaps even stop the disease in its tracks. In a study recently published in STEM CELLS Translational Medicine, a team of University of Michigan researchers describe how they revved up the levels of a protein called IGF-I in a line of neuronal stem cells (NSCs), which resulted in the NSCs producing brain cells that were both resistant to AD and capable of restoring AD-ravaged cells to normal.
AD is an irreversible neurodegenerative disorder affecting an estimated 5.3 million people in the U.S. alone. Patients typically exhibit progressive cognitive decline. Current treatments can slow the symptoms, but the disease is ultimately fatal. Given the prevalence of AD in an increasingly aging population, new therapeutic strategies are urgently needed.
"Neural stem cell transplantation represents an exciting new approach to treating AD," said Eva Feldman, M.D., Ph.D., who led her colleagues in the university's departments of neurology and neurosurgery on the study. "NSCs have a long-term self-renewal capacity, the potential to differentiate into a number of neural cell types and the ability to provide an unlimited source of cells for regenerative medicine."
NSC transplantation has already been shown to improve brain or motor functions after stroke and in Parkinson's disease and ALS. Researchers believe it has the potential to do the same in AD. In fact, recent reports indicate that when human NCS were transplanted into the brains of mice with AD, the animals' cognition improved as did their neuron survival rates and synapse function.
"This further validated our approach and emphasized the need to identify the cell type that can provide the most effective benefit to patients with AD," Dr. Feldman said.
In particular, her group wanted to test what would happen if they enhanced a line of NSCs called "HK532" (produced by Neuralstem Inc.), and engineered the cells to produce a 50-fold increase in insulin-like growth factor-I (IGF-I). IGF-I is a protein that affects multiple cellular behaviors, including proliferation, migration and differentiation. It also blocks the loss of brain cells and has anti-inflammatory effects. Reduced IGF-I levels are associated with cognitive decline; conversely, increased IGF-I in the hippocampus – the brain's memory and learning center – prevents cognitive deficits.
"Give this neuro-protective potential, we hypothesized that an IGF-I enhanced human NSC line would prove advantageous in fighting AD," Dr. Feldman said.
After upping the IGF-I levels of the NSC cells, they tested them in vitro (outside the body) and determined that the protein's addition did not harm normal cell functions, thus demonstrating their safety. At the same time, they found that the NSCs differentiated into a type of neuron targeted by AD, plus they saw an increase in vascular endothelial growth factor levels (a substance made by cells that stimulates new blood vessel formation) and in neuro-protective capacity.
Importantly, when the NSCs were transplanted into AD mice, the researchers found that after 10 weeks the cells had survived in the targeted areas of the brain and were beginning to differentiate into neurons. Dr. Feldman and her team have already started on the next steps to see if the cells can improve Alzheimer's symptoms such as learning and memory deficits in AD mice.
"Overall we believe our findings support moving ahead with developing and more testing of these IGF-I producing NSCs," Dr. Feldman said. "Hopefully this will lead to a safe, effective therapy for AD patients."
"This study suggests that harnessing the benefits of cellular and growth factor therapies together may provide a more effective therapy than single-target drugs, said Anthony Atala, M.D., editor of STEM Cells Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The findings support further development and pre-clinical testing."
The full article, "Human Cortical Neural Stem Cells Expressing Insulin- Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease," can be accessed at http://www.stemcellstm.com.