The first stem cell therapy targeting a major brain disorder, chronic stroke, could begin clinical trials this year if the U.S. Food and Drug Administration approves the request filed in December by stem cell firm ReNeuron in Guildford, England. This latest treatment suggests stem cell therapies are growing not only in number but in ambition.

Chronic stroke, in which patients suffer from permanent infirmity, is the leading cause of adult disability in the developed world. It afflicts 25 million people worldwide, and the number of new cases is rising 7 percent annually, mostly because of an aging population. "Right now there's next to nothing for treating chronic stroke, and what there is addresses the symptoms rather than the cause," says neurologist Justin Zivin of the University of California, San Diego.

Stem cells have the potential to regenerate body parts. In prior stroke studies on animals, stem cells injected into the brain or bloodstream migrated to sites of damage, apparently drawn by signals from damaged cells. This migration may happen because the repair pathways initiated by the damaged cells are similar to pathways triggered during embryonic development, where stem cells are key, explains ReNeuron co-founder and chief scientific officer John Sinden.

A major concern about stem cells centers on how unstable they can become when grown in the lab. ReNeuron can generate large numbers of stable cell lines by engineering cells with a modified version of the gene c-myc. This gene promotes cell division while activating genes that prevent chromosomal abnormalities. The scientists can switch c-myc on or off by introducing or withholding a synthetic compound.

ReNeuron developed cells for brain damage by splicing their modified c-myc into human fetal brain tissue obtained from a U.S. cell bank. They tested 120 neural stem cell lines in the lab for stability and robustness and in animals for the capacity to engraft with minimal immune rejection. Two lines showed potential: ReN001, which ReNeuron is aiming at stroke, and ReN005, which is under research for Huntington's disease.

In studies with rats that experienced stroke, ReN001 significantly improved sensory and motor function. The stem cells probably did not replace the massive number of cells lost during stroke, Sinden clarifies. Rather the cells most likely pumped out chemicals that activated repair pathways, resulting in new blood vessels and brain cells.

If their phase I clinical trial to test the safety and preliminary efficacy of this therapy gains approval, University of Pittsburgh researchers will test the therapy on 10 patients who suffer from chronic ischemic stroke--the most common form, in which clots block blood flow. Ten million to 20 million cells will be implanted directly in the brain through a small hole in the skull, and patients will be monitored over 24 months. ReNeuron has partnered with BioReliance in Glasgow, Scotland, to scale up cell production; the company has roughly one million ReN001 doses currently on hand, Sinden estimates.

Past clinical trials of stem cell therapies for chronic stroke patients used cells derived from tumors in humans and brain tissue from fetal pigs. ReNeuron's fetal cells "are closer to the neurons in [healthy] people than others used before, so they might be more effective," Zivin says. "What ReNeuron has done to create this cell line is ambitious and well thought out," adds neurologist Sean Savitz of Harvard Medical School. Savitz notes, however, that c-myc is associated not only with stem cells and development but also with cancer. "This is definitely not to say that it will promote tumors," he says, but the researchers "will have to continue to convince the scientific community that the cells will not divide unchecked the way they do in tumors."

UPDATE: The FDA has put ReNeuron's request for approval of ReN001 on hold, citing the need for additional information. ReNeuron says that the concerns are readily addressable and that preclinical studies now underway should answer the FDA's questions.