Hope For Successful Alzheimer's Drug Comes After Compound Reverses The Disease In Mouse Models
Researchers at Saint Louis University have successfully reduced the symptoms of Alzheimer's in mice genetically engineered to have Alzheimer's disease (AD). The specific molecular compound that was used in the study, antisense oligonucleotide (OL-1), attacked the most widely-studied cause of AD, the accumulation of amyloid beta protein in the brain.
The over-expression of amyloid beta protein is responsibe for the formation of plaque in the brain. OL-1 was successful in blocking the translation of RNA into amyloid beta protein by decreasing the over-expression of the amyloid beta protein precursor. It thereby normalized the amount of amyloid beta protein in the bodies of mice that were genetically pre-disposed to oversecrete the protein.
Like people who have AD, mice with the disease express elevated levels of amyloid beta protein, as well as increased inflammation and oxidative damage to the hippocampus. Additionally, the mice display memory and learning impairments.
The genetically engineered mice were tested in two groups, one on the OL-1 antisense, and the other on a random antisense, and two groups of 'wild mice' were tested on the OL-1 and random antisense. Both groups of AD mice tested on the OL-1 antisense showed a reduction in amyloid beta protein, a reduction in inflammation and damage to the hippocampus, and a return of their memories and learning abilities.
Researchers also tested the effects of administering the drug through the central nervous system versus intravenously, and determined there was no difference in how the drug performed in either case.
"Our findings reinforced the importance of amyloid beta protein in the Alzheimer's disease process," said Dr. Susan Farr, research professor of geriatrics at Saint Louis University. They suggest that an antisense that targets the precursor to amyloid beta protein is a potential therapy to explor to reversing symptoms of Alzheimer's disease.
The study is published in the May issue of the Journal of Alzheimer's Disease.