The discovery of a new compound could be the key to stopping Alzheimer’s disease from worsening. Researchers from the Sidney Strickland's Laboratory of Neurobiology and Genetics at Rockefeller University will publish their promising new findings in the journal Nature Reviews Drug Discovery in July.
"Our experiments in test tubes and in mouse models of Alzheimer's showed the compound, known as RU-505, helped restore normal clotting and cerebral blood flow. But the big pay-off came with behavioral tests in which the Alzheimer's mice treated with RU-505 exhibited better memories than their untreated counterparts," said Norris S. Strickland, the study’s lead author and director of the Rockefeller laboratory. "These results suggest we have found a new strategy with which to treat Alzheimer's disease."
Researchers treated the brains of mice who had Alzheimer’s with the compound RU-505, which showed less inflammation and improved blood flow compared to mice who went untreated. The mice performed better on memory tests by escaping mazes quicker, which is a characteristic of the disease. RU-505 interferes with amyloid- β, which is a small protein that forms plaques in Alzheimer’s brains, ultimately causing blood clots. The interference, however, stops such clots. RU-505 was discovered after reviewing 93,716 compounds from a library and testing them to amyloid- β.
For over 10 years, researchers have tried different drugs on amyloid- β, but during clinical trials they couldn’t slow Alzheimer’s progression, or they caused serious side effects. By targeting the protein’s ability to bind and clot, this new treatment approach could become a hugely significant moment in finding a cure for those suffering from Alzheimer’s.
"We tested RU-505 in mouse models of Alzheimer's disease that over-express amyloid- β and have a relatively early onset of disease. Because Alzheimer's disease is a long-term, progressive disease, these treatments lasted for three months," said Hyung Jin Ahn, the study’s co-author and research associate in the laboratory. "Afterward, we found evidence of improvement both at the cellular and the behavioral levels."
Alzheimer’s is a type of dementia that causes life-altering problems with memory, thinking, and behavioral changes. Overtime, the condition progressively worsens to the point it becomes severe and interferes with daily tasks. More than five million Americans suffer from Alzheimer’s Disease and every 67 seconds another person in the United States is diagnosed, according to the Alzheimer’s Association. Approximately 500,000 people die each year from Alzheimer’s, which is why an effective treatment is in grave demand.
"While the behavior and the brains of the Alzheimer's mice did not fully recover, the three-month treatment with RU-505 prevents much of the decline associated with the disease," Strickland said.
Rockefeller researchers have already begun to take the next steps towards human trials. The Robertson Therapeutic Development Fund and the Tri-Institutional Therapeutic Discovery Institute are helping to refine RU-505 in order to help the early stages of drug development in order to expedite the process and get it to Alzheimer’s patients as soon as possible.
"At very high doses, RU-505 is toxic to mice and even at lower doses it caused some inflammation at the injection site, so we are hoping to find ways to reduce this toxicity, while also increasing RU-505's efficacy so smaller doses can accomplish similar results," Ahn said.
Source: Ahn HJ, Glickman JF, Strickland NS,, et al. A novel A -fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice. Journal of Experimental Medicine. 2014.