JACKSONVILLE, Fla., July 1, 1999 -- Mayo Clinic Jacksonville scientists have shown that a specially created molecule injected into the belly of a rat can cross the nearly impassable blood-brain barrier and can stop the chemical reaction in the brain that the molecule was designed to impede.
The discovery is an amazing and unexpected finding. It could some day lead to drugs specifically created to fight disease at the molecular level, says Dr. Elliott Richelson.
Richelson and his colleagues in the Neuropsychopharmacology and Neurochemistry labs at Mayo Jacksonville and the Department of Biochemistry and Molecular Biology at Mayo Clinic Rochester described their findings in the June 8 issue of the Proceedings of the National Academy of Sciences.
Richelson has been studying neurotensin, a small piece of protein, or peptide, found in the brain and involved in pain perception and lowering body temperature. For the last few years, scientists worldwide have been testing the theory that interfering with a protein's production on a molecular level might stop it from carrying out its job in humans. Scientists were trying to interfere with protein production by creating special "antisense" molecules designed to block a cell's ability to make specific proteins.
To better understand the brain peptide he was researching, Richelson and his colleagues used peptide nucleic acids (PNAs), a new type of molecule, to create antisense compounds targeting neurotensin. When they injected the PNA antisense molecules into the brains of rats, the molecules worked. They blocked neurotensin's ability to lower body temperature and reduced its ability to block the sensation of pain.
"Then we injected PNA in the belly of the rat to see what would happen, and we got the same result," Richelson says. "Nobody had ever shown that you could inject this type of molecule or any type of antisense molecule in the belly and get a biological response in the brain."