TORONTO — Allelix Biopharmaceuticals Inc.'s long-term association with its research collaborator Eli Lilly Canada Inc. has been expanded, bringing Lilly's total investment in Allelix to more than C$30 million since the partnership began in 1989.

Graham Strachan, Allelix president and CEO, told BioWorld International that, in collaboration with Lilly, the company has discovered and patented Excitatory Amino Acid (EAA) receptors for use in assays in the development of compounds for treatment of a number of diseases, including stroke, dementia, cognitive dysfunction and neurodegenerative disorders. For example, using specific EAA receptors, Allelix has developed proprietary tests to identify compounds that may potentially reduce or even prevent the adverse effects of stroke.

The increased funding means Allelix will expand its EAA project by adding further staff and resources to one relating to neuropeptide Y (NPY) receptors that they are also working on with Lilly Canada, a subsidiary of Indianapolis-based Eli Lilly and Co.

NPY is an important neuromodulator in many neurons and nerve fibers in the brain and periphery and has been implicated in various physiological and pathophysiological processes. Recently, the ob gene product leptin has been shown to suppress the synthesis of NPY in the hypothalamus of the brain, indicating a possible role of NPY in obesity.

The objectives of the expanded Allelix-Lilly research project, which targets eating disorders such as obesity, is to incorporate functional genomics techniques, developed at Allelix, to identify novel molecular targets that will complement the existing program on NPY receptors initiated in 1995.

While these neuroscience programs at Allelix continue to expand, Strachan reported the company would not be proceeding with early-stage development of D4-selective compounds for schizophrenia, which it was pursuing with alliance partner Hoechst Marion Roussel (HMR), of Frankfurt, Germany.

The companies instead will continue discussions regarding other potential applications for their novel D4-selective compounds, which Allelix and HMR have identified as the strategic objective of their collaboration.

The original C$53 million strategic alliance with HMR was struck to discover dopamine D4 receptor-specific compounds for schizophrenia. Chemical candidates from both Allelix and HMR were identified for evaluation in biological assays predictive of anti-schizophrenic behavior.

Dopamine neurons have been shown to be involved in Parkinson's disease and have been implicated in schizophrenia and addictive behaviors. It has been a commonly held theory that in schizophrenia a patient suffers from an abnormally high level of dopamine in the system. Expectations therefore have run high that a selective D4 dopamine receptor antagonist might improve the pharmacological treatment of patients with schizophrenia.

However, data from recent clinical trials have reported disappointing results, said Strachan, casting some doubt on the efficacy of D4 dopamine receptor antagonists. HMR is adopting a wait-and-see policy until the results of ongoing multicenter trials from other organizations are published. Although the schizophrenia research project is now on hold, the companies are continuing their discussions regarding other potential therapeutic applications, including the treatment of attention deficit hyperactivity disorder, epilepsy and substance abuse.

Allelix and Hoechst Marion Roussel will continue assessing the viability of future collaborations to develop compounds for these applications.

With these alliances, Allelix maintains and expands an active program in the area of neuropharmaceuticals, Strachan added. The company now has nine products in various stages of clinical development, including two migraine drug treatment candidates that demonstrate highly specific activity for serotonin 5HT1 receptors. In testing so far, the molecules have shown to be more potent than available therapeutics, with none of the significant cardiovascular side effects often observed in these current therapies.

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