BioWorld International Correspondent
LONDON - ReNeuron plc submitted the additional data requested in the investigational new drug file for its stem cell treatment for stroke, keeping it on track to be the first to carry out an FDA-approved trial of neural stem cells in a major neurological disorder. The file, originally submitted a year ago, was put on hold in January.
The company was asked to complete a number of further preclinical studies, the most important of which was one examining the long-term safety profile of the product, ReN001 in a specialized rodent stroke model. The data from the study showed no unusual or adverse safety effects in either control or treatment groups.
John Sinden, chief scientific officer, said the company was "very confident" that it had met all the FDA's requirements. "We have not just taken advice from our [own sources], we've spoken to key senior FDA people and FDA lawyers," he told BioWorld International.
Getting the go-ahead this time is critical for the company, which had cash of £5.7 million (US$8.4 million) at the end of September, enough to last until the third quarter of 2008.
If the response is positive, and pending local ethical approval, the 10-patient trial will go ahead under Douglas Kondziolka at the University of Pittsburgh Medical Center. The treated patients will be in a stable condition four months post-stroke and carefully selected to ensure they have no other underlying or pre-existing neurological pathologies. The trial will look at a number of measures of disability.
Guildford, UK-based ReNeuron has contacted the UK Medicines and Healthcare Regulatory Agency to discuss the requirements for conducting a UK trial. "We talked to them when we were first interested in getting into the clinic over two years ago, but they were not able to regulate this type of product," Sinden said. "Talking to them a month ago, it is obvious they have moved on really well, and we got a very good reception."
To back a move into the clinic in the UK, the company has appointed Philip Bath, professor of stroke medicine at Nottingham University, onto its clinical advisory board. Bath is an expert in drug trials in stroke at both preclinical and clinical level.
Although eager to do a trial in the UK, Sinden said ReNeuron will wait to see what happens with the FDA application before proceeding further.
ReN001 is a clonal neural stem cell line generated from fetal brain tissue. The cell line is expanded at an industrial scale using the company's c-mycER gene, which is then switched off prior to transplantation, preventing further proliferation. The product improves functional recovery in rat models of stroke.
The patented c-mycER stem cell expansion technology has been used to generate stable human pancreatic cell lines for Type I diabetes, also. The cell lines form islet cell clusters that secrete insulin in response to glucose concentrations, and express phenotypic markers for insulin-producing islet cells.
To back up that advance, ReNeuron recently acquired AmCyte Inc., a development stage cell therapy company based in Santa Monica, Calif. The company is working to combine its pancreatic cells with AmCyte's cell encapsulation system, which has been in clinical trials using islet cells from human cadavers.
ReNeuron hopes to overcome the shortage of donated pancreatic tissue from which to derive islet cells, and avoid the immune reaction prompted when naked islets are transplanted into diabetes patients.