LONDON - ReNeuron Ltd. said it is on target to carry out clinical trials of clonal stem cell transplants for the treatment of stroke by the end of 2000.

The London-based company has succeeded in producing clonal cell lines from human fetal brain cells. Fetal cells, grown in culture, have an oncogene inserted that allow them to become immortal. Not all cells take up the gene, and ReNeuron has developed a process for identifying cells containing the gene and expanding them into a clonal cell line.

Martin Edwards, CEO, told BioWorld International, "We have successfully overcome the regulatory, clinical and practical issues that needed to be dealt with in order to develop human cell lines."

Specifically, it has secured a supply of human tissue in line with ethical and regulatory guidelines, succeeded in infecting human cells with immortalizing oncogenes, and developed methods to characterize the human cell lines.

"We've got mouse cell lines which are brilliant, where we can consistently infect them with the immortalizing oncogenes, and which work very well in animal models of stroke," Edwards said. "We are growing human cells using the same technology but at present the take-up of oncogenes occurs at a low frequency. It is now a matter of getting the gene in consistently"

Once immortalized cell lines are established, they can be grown and expanded indefinitely, leading to a continuous supply of identical cells. The lines are conditional, which means they divide at lower temperatures, while at body temperature they stop dividing, a feature which ReNeuron says eliminates the risk of tumor formation from implanted cells.

ReNeuron has worked extensively with a mouse cell line, MHP36, showing functional recovery in rats with ischemic hippocampal damage. The cells migrate from the site of insertion to the site of damage, differentiating into both neurons and glia and repairing the behavioral deficit. The cells also reduce paralysis after spinal cord irradiation, and improve cognitive function in aged rats, a model of Alzheimer's disease.

Edwards, who was previously head of drug development at Novo Nordisk, hopes the company's first clinical trial will be in stroke, though he said the indication will depend on the properties of the first cell lines to be immortalized. "We expect the initial trial to be in a dozen patients within a few weeks to a few months of the stroke. This will be a safety trial, but obviously we want to show an effect, and so we need the patients to be stable." Cell transplants can be injected under local anesthetic.

The company was founded in 1997 by John Sinden, Helen Hodges and Jeffrey Gray of the Institute of Psychiatry in London. It received #5 million from the Merlin Fund at the end of 1997 and now needs to raise more money. "This is exciting science with a big market potential and we believe we will be able to raise more funding," Edwards said.

The company has also established a testing service allowing other companies access to its models of neurological diseases. "We set up the service because of requests to use our models and because investors like to see an income stream."