In a breakthrough which could help in the treatment of Alzheimer’s disease and chemotherapy-resistant forms of cancer, researchers from Cornell University have discovered a way to get past the blood-brain barrier and safely deliver drugs directly into the brain itself.
For more than 100 years, doctors and scientists have struggled to treat brain disorders and other types of diseases that required drugs to be delivered across the barrier, a layer of specialized cells known as endothelial cells designed to protect the brain from undesirable substances.
The barrier, which lines the brain’s blood vessels, can selectively allow molecules essential to normal body function – molecules such as amino acids, oxygen, glucose, and water – entry into the brain. Hoping to capitalize on this behavior, the Cornell researchers found that Lexiscan, an FDA-approved drug, activates receptors that are expressed on the endothelial cells.
Using this knowledge, Margaret Bynoe, associate professor in the Department of Microbiology and Immunology in Cornell’s College of Veterinary Medicine, and her colleagues were able to deliver both chemotherapy drugs and larger antibodies that bind to Alzheimer’s disease plaques directly into the brains of mice.
Discovery could lead to new cancer, Alzheimer’s, Parkinson’s treaments
To test their technique, which was described in the April 4 edition of The Journal of Clinical Investigation, Bynoe, postdoctoral associate Do-Geun Kim and their fellow researchers created a model of the blood-brain barrier using human primary brain endothelial cells. Their experiments found that Lexiscan had the same effect on the model barrier as it did in mice.
“We can open the BBB for a brief window of time, long enough to deliver therapies to the brain, but not too long so as to harm the brain,” Bynoe, senior author of the study, explained in a press release. “We hope in the future, this will be used to treat many types of neurological disorders.”
She and Kim found that a protein called P-glycoprotein is highly expressed on brain endothelial cells, and is responsible for preventing most of the drugs delivered to the brain from getting past the barrier. Lexiscan, however, activates receptors on the endothelial cells, down-regulating the protein expression and temporarily switching off the barrier so that it can get past it.
“We demonstrated that down-modulation of P-glycoprotein function coincides exquisitely with chemotherapeutic drug accumulation” in the brains of mice and across an engineered BBB using human endothelial cells,” said Bynoe. “The amount of chemotherapeutic drugs that accumulated in the brain was significant.”
This protein is also expressed by several forms of cancer, making them chemotherapy-resistant, the authors said. By building on their findings, Bynoe believes that it may someday be possible to modulate these receptors to regulate P-glycoprotein in these tumor cells. The study’s findings could lead to new treatments for these cancers, as well as for conditions such as Alzheimer’s and Parkinson’s diseases, autism, and other brain-related disorders.
—–
Image credit: Thinkstock
Comments