Combination Therapy Halts, Reverses Symptom Of Alzheimer’s Disease In Transgenic Mice
A combination approach for arresting and reversing amyloid plaque buildup in the brain has proven effective in studies of transgenic mice with this feature of Alzheimer’s disease, said researchers from Baylor College of Medicine in a recent issue of The Journal of Neuroscience.
“There are many ways to delay the appearance of amyloid plaques in mice, but now with a combination approach we can actually remove plaques that had formed prior to treatment,” said Dr. Joanna Jankowsky, assistant professor of neuroscience, neurology and neurosurgery at BCM.
Amyloid plaques form when Abeta peptide collects into fibrous deposits between nerve cells in the brain. Many scientists believe that the aggregation of Abeta may play a key role in Alzheimer’s disease, and that arresting its production or clearing away its aggregated deposits could reverse symptoms such as memory loss and mental deterioration in humans, Jankowsky said.
She and her colleagues studied mice that develop amyloid plaques similar to those found in human patients, and started their combination treatment after the mice had formed roughly the same degree of amyloid pathology as seen in patients with mild to moderate Alzheimer’s disease.
By suppressing the production of Abeta peptide, they were able to stop new plaques from forming and keep existing plaques from getting worse. However, when the mice were given an Abeta-antibody therapy in combination with Abeta suppression, there was a noticeable reduction in plaque load. After just a few months of treatment, the combination therapy resulted in a 50 percent reduction in plaque burden compared to the start of treatment.
Working to improve human therapies
“Right now this approach to treatment is only feasible in laboratory mice. Our hope is that the animal studies will help us understand how to improve human therapies in the future,” said Jankowsky, who is also a faculty associate of the Huffington Center on Aging at BCM.
Researchers learned the Abeta antibody crossed the blood-brain barrier (a natural formation that protects brain cells from toxic chemicals) in small amounts and then bound to the plaques. This allowed microglia (immune defense cells in the brain that engulf and destroy dead cells and debris) to engulf and discard the plaques.
“The combination is the key. By suppressing Abeta production, we allow the antibody to have a more significant impact,” said Jankowsky. “In other words, it’s easier to clean up a flood once it stops raining.”
Others who contributed to the study include Allan Wang, Rice University and BCM; Dr. Pritam Das, Mayo Clinic Florida, Jacksonville; Dr. Robert C. Switzer III, Neuroscience Associates, Knoxville, Tenn., and Dr. Todd E. Golde, University of Florida, Gainesville, Fla.
This work was funded by an Alzheimer’s Association grant through The Straus Family Fund, the National Institute on Aging, and a New Innovator Award from the Office of the Director of the National Institutes of Health.
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