Drug "fixes leaks" in the blood-brain barrier to treat Alzheimer's
Scientists have synthesized molecules to restore proper functioning of the brain's protective barrier and prevent the development of neurological diseases. The study was published in the journal Nature Communications.Researchers from Stanford University synthesized molecules that affect the blood-brain barrier (BBB) and restore its normal function. The treatment can prevent a variety of neurological diseases associated with the malfunctioning of the BBB - multiple sclerosis, Alzheimer's disease and brain cancer.
The blood-brain barrier is a semi-permeable membrane inside the blood vessels that feed the brain. When it is normal, it prevents pathogens and toxins from entering the brain while ensuring that the brain is supplied with nutrients. If the functioning of the hEB deteriorates, cancer cells that have crossed the barrier can grow into tumors, and excess white blood cells can cause an autoimmune reaction and lead to the development of multiple sclerosis.
Stanford researchers studied molecules that can "restore isolation in the leaky barrier." They focused on the functioning of the Wnt signaling pathway, which previous studies have shown helps maintain the functioning of the HEB. The researchers identified an L6-F4-2 molecule that activates the FZD4 receptor in cerebral blood vessel endothelial cells. Exposure of the molecule to the receptor resulted in 100 times more effective Wnt signaling.
Scientists tested the effect of L6-F4-2 on mice with a genetic mutation that makes the GEB (retinal barrier protecting the retina) analog permeable to toxins. Exposure to the drug made the blood vessels in the treated mice denser and less permeable than before. In another experiment, a similar treatment strengthened the blood-brain barrier around the cerebellum in genetically deficient mice.
In another experiment, scientists investigated the effect of the molecules on the development and course of stroke. Analysis showed that injecting L6-F4-2 into mice reduced the severity of the disease, improved animal survival, and helped repair leaks that occurred in blood vessels.
A ruptured blood-brain barrier is a common pathway for many brain diseases, so the ability to isolate the barrier has been a long medical goal.
Although clinical trials will be needed to confirm the efficacy and safety of such a therapy in humans before it can become fully functional in medicine, researchers believe that the current results offer hope for the future treatment of many neurological diseases.