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Biotech / Medical : Gliatech (GLIA) -- Ignore unavailable to you. Want to Upgrade?

To: Dr. John M. de Castro who wrote (1442)	3/2/2000 10:15:00 PM
From: Dr. John M. de Castro	Read Replies (1) \| Respond to of 2001

More on the rationale for GLIA's Glycine Transporter program. Best regards John de C D-Cycloserine Can Improve Negative Symptoms Carl Sherman, Contributing Writer [Clinical Psychiatry News 26(7):25 1998.] TORONTO -- D-cycloserine, a partial agonist of the amino acid glycine, may alleviate negative symptoms and improve cognitive function in schizophrenia, Dr. Donald C. Goff said at the annual meeting of the American Psychiatric Association. The compound appears to act by stimulating receptors of glutamate, the principal excitatory neurotransmitter in the brain and one that plays a major role in cognitive functions, said Dr. Goff of Harvard Medical School, Boston. Several earlier trials of glycine have demonstrated "impressive" improvements in negative symptoms and little effect on positive symptoms of schizophrenia. The substance is difficult to administer, however. Because it penetrates the blood-brain barrier poorly, high doses (in the range of 60 g/day) must be used, he said. D-cycloserine, on the other hand, crosses the blood-brain barrier easily. As a partial agonist, the compound at low concentrations acts like glycine at glutamate receptor sites. Dr. Goff described an 8-week, double-blind, placebo-controlled trial of D-cycloserine in which 23 schizophrenic patients received 50 mg/day of the drug, and 23 received placebo. All patients met criteria for "deficit syndrome": They had marked, persistent negative symptoms, with a score of 30 or higher on the Scale for Assessment of Negative Symptoms. The patients were predominantly male and had chronic disease, with a mean disease duration of 20 years. Improvements in negative symptoms as measured by the scale were significantly greater in the treated group: A 23% decline from baseline in the treated group was seem, compared with a 7% decline in the controls. When divided into responders and nonresponders, 61% of the D-cycloserine-treated patients were responders, compared with 26% of the placebo group. Dropout rates were high in the medication group: Seven patients receiving D-cycloserine dropped out, compared with one in the placebo group. In roughly half the cases, this appeared to reflect the efficacy of the drug. Patients were removed from the study to vacation with their families, who "wanted to take advantage of their improved condition," Dr. Goff said. Further analysis showed that gains were greatest in the area of blunted affect. There were trends for improvement in anhedonia and associativeness, but no differences in apathy, attention, or alogia. No changes were evident on neuropsychological testing. The drug appeared to have no effect on symptoms unrelated to deficit syndrome; psychosis, depression, and parkinsonism did not improve, Dr. Goff said.