Researchers funded by the Alzheimer’s Drug Discovery Foundation have identified a promising new drug that prevents the formation of abnormal blood clots in the brain, reduces cerebral inflammation and improves memory in mice with Alzheimer’s disease. The drug, RU-505, is a synthetic compound identified from an initial pool of nearly 95,000 drug candidates.
Neurons cannot function without a regular supply of blood, and researchers now know that developing treatments that protect neurons from damage and death is critical to finding a cure for Alzheimer’s. Patients with Alzheimer’s often suffer from persistent blood clots in the brain, leading scientists to believe that these clots may be one of the malefactors behind Alzheimer’s disease.
The Alzheimer’s Drug Discovery Foundation co-funded the experiments, which were conducted by Sidney Strickland’s Laboratory of Neurobiology and Genetics at Rockefeller University in New York City, with a $100,000 grant in 2008 and a $150,000 grant in 2010.
The compound appears to work by interfering with the interaction between beta-amyloid and fibrinogen (a clotting protein present in the blood). Strickland’s laboratory previously demonstrated that this interaction leads to the formation of abnormal blood clots.
By identifying a drug that inhibits the beta-amyloid/fibrinogen interaction, researchers were able to protect against abnormal clotting and reduce cerebral inflammation, a hallmark of Alzheimer’s disease.
For nearly two decades, the bulk of Alzheimer’s drug research has targeted beta-amyloid. By focusing instead on the protein’s tendency to bind to fibrinogen, this new research offers a fresh approach to treating Alzheimer’s disease.
RU-505 did not fully eradicate Alzheimer’s in mice trials, but it prevented much of the cognitive decline associated with the disease. Researchers are now taking steps to refine the compound before testing it in patients with Alzheimer’s.
This exciting research is just one example of the incredible impact early funding from the ADDF can have on Alzheimer’s drug development—advancing promising science that might otherwise be stuck in the concept phase and paving the way for new treatments for Alzheimer’s disease.
Strickland's research was published in the Journal of Experimental Medicine.