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2010 Grants - Karande
Study of Tight Junction Binding Peptides for Drug Delivery Across the BBB
Pankaj Karande, Ph.D.
Rensselaer Polytechnic Institute
Troy, New York
2010 New Investigator Research Grant
One of the biggest challenges for Alzheimer drug research is to develop compounds that effectively cross the blood-brain barrier. This barrier surrounds the brain and protects it from foreign substances in the blood. Many methods of delivering drug compounds to the brain are risky, because they make the blood-brain barrier too permeable and expose the brain to harmful compounds. Other methods are expensive and impractical for a chronic disease like Alzheimer's, which may require multiple drug delivery treatments.
Pankaj Karande, Ph.D., and colleagues have begun testing a delivery method across the blood-brain barrier that may prove safe and cost-effective. This method involves using inexpensive peptides (protein fragments) that bind to a protein called claudin 5. Claudin 5 helps form protein complexes called "tight junctions" that regulate transportation across the blood-brain barrier. By binding to claudin 5, the peptides should be able to create a temporary gap in the blood-brain barrier through which drug compounds could enter the brain.
For this proposed grant, Dr. Karande and colleagues will design and test several peptides that can bind to claudin 5. They will then test the ability of these compounds to penetrate a model blood-brain barrier engineered from different human cells. The researchers will also determine if the peptide-induced permeability of their blood-brain barrier is reversible. They want to be certain that their method does not keep living blood-brain barriers "open" and exposed for too long a period of time.
The results of this effort could provide a practical and safe method for administering novel Alzheimer drug therapies.