FIRST POTENT ANTAGONIST TO SUBSTANCE PPfizer Inc. researchers describe in today's issue of Science thefirst potent antagonist to substance P (SP), a proteinneurotransmitter, vasodilator and immune response activator.The antagonist could yield an understanding of SP's manyphysiological roles and lead to drugs to counteract SP's harmfuleffects.
SP also leads to smooth muscle contraction, stimulatessalivation and promotes pain transmission through nerves. The11-amino-acid-long peptide is a tachykinin. Specificphysiological responses of tachykinins have been difficult toidentify.
Although researchers have tested other potential SP agonistsand antagonists, none has had the specificity or potency neededto pinpoint SP's role. SP itself is difficult to study due to itssmall size and instability.
Pfizer's non-peptide compound CP-96,345 may be the key tosolving the puzzle of how SP works. Pfizer scientists showedthat CP-96,345 blocks binding of SP to its brain receptor NK-1.They also showed that CP-96,345 blocks SP's ability tostimulate salivation in anesthetized rats.
CP-96,345 was discovered using a chemical file-screeningapproach. The scientists said it is premature to use molecularmodeling or to design SP-like drugs de novo. --Carol TalkingtonVerser
GENE CLONED FOR MISSING MD PROTEIN
Scientists at the Baylor College of Medicine in Houston reportedThursday in the journal Nature that they cloned and expressedin cell culture the gene for a protein that is lacking in patientswith Duchenne's muscular dystrophy (DMD). This could lead toa possible gene therapy to correct the condition.
Researchers previously were able to clone only pieces of thegene because of its large size, said Cheng Chi Lee, the paper'slead author. His laboratory is trying to insert the gene into aspecial breed of mice that mimics the muscle wasting of DMD.If the inserted gene heals the mice, Lee's group plans torequest permission from federal agencies to conduct genetherapy in human patients.
The advance "extends the promise of a DMD therapeutic," saidNigel Fleming, chairman of Genica Pharmaceuticals Corp. ofWorcester, Mass. Genica, which focuses its research onneuromuscular and neurological diseases, holds an exclusivelicense to a broad pending patent covering the DMD gene andrelated diagnostics and therapeutics.
Harvard Medical School applied for a patent based on thediscovery of the gene by Louis Kunkel. Lee said BaylorUniversity does not intend to file for a patent based on theirdiscovery. H Carol Ezzell
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