LONDON - Cerebrus Ltd., a specialist in central nervous system (CNS) disorders, has set up a joint venture with an academic partner to explore the use of sodium channel blockers for treatment of stroke and other neurological disorders.

Under the agreement with the Wolfson Institute for Biomedical Research, Cerebrus will fund the new company, called CereXus, for three years. No financial details were given, but Cerebrus said the deal is subject to achievement of certain research milestones.

Colin Dourish, research director of Cerebrus and chairman of CereXus, told BioWorld International the partners decided to set up a company rather than a more straightforward research collaboration “because a joint venture was the vehicle that best suited both parties and will enable us to bring out the best value of the deal.“

CereXus initially will be owned equally by the partners, but “it depends on inputs if that stays the same,“ Dourish said. He described the CereXus joint venture between an emerging company and a research institute as a unique approach to drug discovery.

“Although initially we are talking about a short-term collaboration with milestones, we see this as a long-term project, which is why we decided to set up the joint venture company,“ Dourish observed.

The Wolfson Institute, based at University College London, was founded in 1996 by Salvador Moncarda, former director of research at the London-based pharmaceutical company Wellcome plc. Moncarda, who was first to propose the biological role of nitric acid, was joined by colleagues who left Wellcome when it merged with London-based Glaxo plc.

The institute was set up specifically to capitalize on the increasing amounts of money that pharmaceutical and biotechnology companies are putting into external collaborations. When the building of its research facilities is completed next year, the institute is expected to employ 300 scientists.

At the time of its takeover by Glaxo, Wellcome had a program looking at the use of sodium channel blockers in the treatment of stroke and had taken one compound, BW619, into Phase I/II trials. These were unsuccessful because of side effects such as hallucinations.

When the research portfolios of the two were merged, Glaxo dropped the Wellcome program in favor of its own work on glutamate blockers. Glutamate is a major neurotransmitter, whose excessive production following stroke causes neuronal death.

Sodium Channel Blockers May Protect Neurons

“Although there is no direct clinical data showing sodium channel blockers work in stroke, the attraction to us is that there is increasing evidence they would be neuroprotective,“ Dourish said. He pointed out the development of neuroprotectants to reduce the brain damage caused by stroke is a serious unmet medical need, with no such drugs currently available.

“CereXus believes that early intervention with sodium channel blockers has the potential to stop the event cascade set in motion by stroke which leads to neuronal death and permanent brain damage,“ Dourish added.

While BW619 is not part of the collaboration, the academic partners “have good ideas for other compounds and believe they know why BW619 was hallucinatory,“ he said.

The discovery of new compounds will be carried out at the Wolfson Institute and the drug candidates will be tested in Cerebrus' animal models of stroke. CereXus also will look at potential applications of sodium channel blockers for pain and drug dependency.

“We expect the initial compounds to be ready for the clinic within three years,“ Dourish said.

Cerebrus, based in Wokingham, U.K., has programs in a range of CNS disorders, including anxiety, Parkinson's disease, epilepsy and obesity. In March 1998 the company raised £10.5 million in a private funding round. It plans to go public within the next 12 months. *