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SIBIA Reports Prolonged Cognitive-Enhancing Effect of Its Lead Nicotinic Acetylcholine Receptor Compound in Pre-Clinical Models of Parkinson's Disease Source: PR Newswire LA JOLLA, Calif., March 12 /PRNewswire/ via Individual Inc. -- In a poster presented at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Meeting in San Diego, scientists from SIBIA Neurosciences, Inc. (Nasdaq-NNM: SIBI) and the Allegheny University of the Health Sciences reported that SIB-1508Y, one of SIBIA's proprietary neuronal nicotinic acetylcholine receptor agonists, demonstrates a prolonged reversal of cognitive deficits in a primate model of the cognitive deficits in Parkinson's disease. Based on the data from these and other studies, SIBIA believes SIB- 1508Y (now in Phase I clinical trials) could offer a new approach to the treatment of Parkinson's disease with distinct advantages over existing Parkinson's disease therapies because of its ability to reduce both cognitive and motor deficits. It is now recognized that cognitive impairment is a serious and frequent symptom in many Parkinson's patients, but no treatment addresses this aspect of the disease. In the studies reported by G. Kenneth Lloyd, Ph.D. and Frederique Menzaghi, Ph.D. of SIBIA and Jay Schneider, Ph.D. of the Allegheny University of the Health Sciences, monkeys were administered low doses of the neurotoxin MPTP to induce the same cognitive deficits observed in Parkinson's patients, but not the severe motor symptoms. MPTP selectively kills the neurons that are also lost in Parkinson's disease, and at higher doses induces a Parkinson's-like syndrome, complete with motor dysfunction, in both animals and humans. Treatment with SIB-1508Y reversed the cognitive deficits in the monkeys, which were assessed by different tests of cognitive performance. Notably, this effect appeared to increase up to 48-hours post dosing and was long-lasting (up to 28 days after a single dose of SIB-1508Y). The rapid onset and long duration of these cognitive effects in the primates suggest two mechanisms -- an initial release of the neurotransmitter acetylcholine, which has been confirmed by other studies, and a possible trophic effect currently under investigation. Parkinson's disease is characterized by the degeneration of catecholamine neurons, especially dopamine neurons, as well as a substantial (approx. 50%) loss of acetylcholine in the cortex and hippocampus. SIB-1508Y stimulates dopamine release in the striatum and limbic system and acetylcholine release in the frontal cortex and hippocampus (but not the striatum). Thus, SIB-1508Y addresses major neurochemical deficits which occur in Parkinson's disease. While the positive effect of SIB-1508Y in the low-dose MPTP model is consistent with the compound's mechanism, the duration of the effect is especially intriguing. This particular finding suggests that SIB-1508Y may induce long-lasting benefits as well as exhibiting symptomatic effects. No other compound has generated such a marked and long-lasting effect in this model of the cognitive deficits of Parkinson's disease. In earlier pre-clinical studies, SIB-1508Y ameliorated the severe motor dysfunction seen in high-dose MPTP-treated monkeys. It also potentiated the motor effects of levodopa and certain other marketed antiparkinsonian drugs in MPTP-treated monkeys. Thus, SIBIA believes SIB-1508Y may have both an intrinsic activity in the treatment of the motor symptoms of Parkinson's disease and a potentiation of levodopa in more severe patients. SIBIA Neurosciences, Inc. is engaged in the discovery and development of novel, small molecule therapeutics for treating disorders of the nervous system based on its unique approach to characterizing the molecular processes involved in such disorders. SIBIA is focusing its efforts on developing compounds for the treatment of Parkinson's disease, Alzheimer's disease, stroke, head trauma, epilepsy, chronic pain, schizophrenia and other disorders. The Company currently has collaborations with Eli Lilly and Company, Novartis (formerly CIBA-GEIGY Limited), Bristol-Myers Squibb Company and Meiji Seika Kaisha, Ltd. This press release contains forward-looking statements that involve risks and uncertainties. As a result, actual results could differ materially from those discussed herein. These risks and uncertainties include SIBIA's early stage of development, the new and uncertain state of SIBIA's technologies, SIBIA's future capital needs and the uncertainty of receiving additional funding, uncertainties regarding patents, proprietary rights and regulatory matters, and other research, development and market risks. These and other risks and uncertainties are more fully set forth in SIBIA's Prospectus included in its Registration Statement on Form S-1 filed in connection with its initial public offering, as well as in SIBIA's most recently filed Form 1O-Q. SOURCE SIBIA Neurosciences, Inc. /CONTACT: Michael J. Dunn, Vice President, Business Development of SIBIA, 619-452-5892, ext. 223/ (SIBI) CO: SIBIA Neurosciences, Inc. ST: California IN: MTC SU: KS-CW -- LAW026 -- 4261 03/12/97 07:01 EST http://www.prnewswire.com [03-12-97 at 12:00 EST, PR Newswire]