Enzyme delivered through the bloodstream corrects deficiencies in the brain
The blood brain barrier is generally considered an obstacle to delivering therapies from the bloodstream to the brain. However, University of Iowa researchers have discovered a way to turn the blood vessels surrounding brain cells into a production and delivery system for getting therapeutic molecules directly into brain cells.
Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases.
The findings, which were published Sept. 13 in Nature Medicine's Advance Online Publication (AOP), could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases.
"This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain," said lead investigator Beverly Davidson, Ph.D., UI professor of internal medicine, neurology, and molecular physiology and biophysics. "This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases.
"In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons," she added.
Lysosomal storage diseases are individually quite rare, but as a group they affect approximately 1 in 8,000 live births. The diseases are caused by deficiencies in enzymes that break down larger molecules. Without these enzymes, the large molecules accumulate inside cells and cause cell damage and destruction.
Enzyme replacement therapy has been successful in treating one form of lysosomal storage disease called Gaucher disease. However, storage diseases that affect the central nervous system remain untreatable because it has not been possible, to this point, to get the missing enzymes past the blood-brain-barrier and into the brain.