JACKSONVILLE, Fla., May 9, 2001 -- The United States Patent Office has issued a
patent to Mayo Foundation for Medical Education and Research for a new amino
acid that may be useful in the treatment of schizophrenia and Parkinson’s
disease. The amino acid, called neo-tryptophan, was created by a team of Mayo
researchers led by Elliott Richelson, M.D.; Yuan-Ping Pang, Ph.D.; and Daniel
McCormick, Ph.D. Other co-inventors on the patent are Mona Boules, Ph.D.; Abdul
Fauq, Ph.D.; Beth McMahon, Ph.D.; and Bernadette Cusack. The patent covers the
amino acid and any peptide that contains it.
Since the early 1980s scientists have suspected that neurotensin, a peptide
comprised of 13 amino acids that is present in the brain, is a natural
anti-psychotic. About 15 years ago, Dr. Richelson, a psychiatrist and
neuropsychopharmacologist, became intrigued with the idea of developing
neurotensin-like compounds as possible novel anti-psychotic drugs. When
introduced into the brain, these neurotensin analogs would activate neurotensin
receptors. Unlike neurotensin itself, these analogs would not be as susceptible
to enzymatic degradation and would therefore have longer-lasting effects.
Richelson and his colleagues began to change systematically the sequence of the
8-13 amino acid portion of the molecule. In the process of developing about 80
different neurotensin 8-13 analogs, they discovered some features of the
molecule conferred better activity at a human neurotensin receptor than at a rat
receptor. Specifically, they figured out the structure of a substitute for the
tyrosine in the 11th position of the molecule that would fit better into the
human receptor. They created an amino acid similar to tryptophan that had the
right three-dimensional configuration to replace the tyrosine. Dubbed
neo-tryptophan, this new amino acid, when it was substituted into the peptide,
markedly increased binding of the peptide to the human receptor.
“As a clinician, I know there is a definite need for new drugs to treat
schizophrenia or Parkinson’s disease,” says Dr. Richelson. “So, we are working
hard to get where we can test whether one of our compounds has clinical
usefulness.”
Dr. Richelson is seeking Food and Drug Administration (FDA) approval to begin
testing a neo-tryptophan containing peptide as a drug for treating schizophrenia
and Parkinson’s disease. He says this peptide also has analgesic properties and
lowers body temperature, so researchers are interested in testing them to
preserve neurons in the brain after an anoxic event such as cardiac arrest. He
hopes clinical trials in human control subjects may be underway by the end of
the year.
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