Eukarion's EUK-134 Protects Against Neuronal Damage in Seizure Model.

BEDFORD, Mass.--(BW HealthWire)--Aug. 17, 1999--

Eukarion, Inc. today announced the publication of a study using the company's EUK-134 compound, a low molecular weight synthetic catalytic scavenger (SCS), in an animal model of epilepsy.

The study is being published in today's issue of the Proceedings of the National Academy of Sciences.

EUK-134 catalytically mimics the activity of two enzymes, superoxide dismutase and catalase, used by the body to protect tissue against toxic compounds known as reactive oxygen species (ROS). ROS are normal byproducts of cellular metabolism but, when injury occurs, the body's ability to neutralize ROS is overwhelmed and significant tissue damage results.

Although it has generally been believed that the neuronal damage which occurs during seizure is at least in part ROS-induced, this relationship had not been clearly established in vivo. In this study, scientists at Eukarion and the University of Southern California (USC) unambiguously demonstrated that oxidative stress precedes neuronal damage in a rat model for temporal lobe epilepsy. Furthermore, they showed that EUK-134 suppressed oxidative tissue damage and, consequently, inhibited neuronal death.

The animals were treated with kainic acid, an excitotoxin known to induce recurrent seizures, and either EUK-134 or saline. Another group received EUK-134 without kainic acid pretreatment. Following sacrifice, brain sections were evaluated for protein oxidation, stress-related gene responses and evidence of neuronal cell death. Together, the results of these tests convincingly demonstrated the role of ROS in neuronal cell damage and death in this seizure model.

In addition, the group treated with EUK-134 had significantly less neuronal damage and cell death than did either the kainic acid-treated or control groups. Further, the EUK-134 treated group had significantly less chemical evidence of oxidative stress-related responses than did the other groups. In the group receiving EUK-134 without kainic acid, no changes were observed.

"These results provide further evidence that ROS play a causal role in seizure-induced neuronal damage and support previous studies that have demonstrated the ability of SCSs such as EUK-134 to mitigate ROS-induced cell damage and death," said Michel Baudry, Ph.D., Professor of Biology and Neurobiology at USC and senior author of the study.

"More broadly," adds Susan R. Doctrow, Ph.D., Vice President of Research at Eukarion and a co-author, "these data reinforce our view that the SCS compounds should be useful in the treatment of a variety of neurological diseases involving oxidative stress." The company's SCS compounds have also been successfully tested in models of stroke, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In addition, they have been found effective in models for myocardial infarction, adult respiratory distress syndrome, allergy and lupus.

Eukarion, Inc., located in Bedford, MA, is a privately held biopharma- ceutical company formed in 1991 to develop proprietary therapeutic agents directed against intracellular targets for the treatment of human disease. The company's principal focus is on its patented synthetic catalytic scavenger (SCS) technology for the treatment of conditions related to oxidative stress. Eukarion also has proprietary technology for the modification of antibodies and other proteins to facilitate their passage across cell membranes and their interaction with specific intracellular targets.