Approval granted for gene therapy Alzheimer's study.

Gene therapy maker Ceregene Inc. has received permission from the Food and Drug Administration to run a new study that calls for injecting critical genes directly into the brains of Alzheimer's patients.

Jeffrey M. Ostrove, president and chief operating officer of the San Diego-based company, plans a six-month study testing 30 to 40 Alzheimer's patients starting in early 2005.

The study aims to lower the loss of cognitive functions, a trademark of the incurable neurodegenerative disease.

Alzheimer's affects 4.5 million people in the United States, and 16 million people worldwide, and its numbers are expected to grow with the rise of the aging population.

Dr. Mark Tuszynski, a neurologist at UC San Diego, recently published preliminary results from the first gene therapy study that began in April 2001.

Gene therapy typically works by introducing a benign virus or "vector" to deliver therapeutic genes inside the patient's cells.

In the first study, doctors removed skin cells from eight patients and genetically modified them so they would secret a protective substance called nerve growth factor, then injected them into the brain.

Two patients moved as the cells were being injected during surgery, resulting in bleeding of the brain that led to the death of one five weeks later. The other patient recovered.

Ostrove said patients are often kept awake during neurosurgery, but the problems happened when the patients moved their heads.

The problems led to a change in the study methods: Participants were put under anesthesia. The six remaining people in the study showed no problems. Preliminary findings suggested that the six had a 50 percent lower rate of annual decline of their cognitive functions, Ostrove said. Drug therapy, he said, did not fare as well.

"Current treatments have minimal effects," Ostrove said.

The next planned trial uses Ceregene's "one-size-fits-all" compound, CERE-110, which is not made from individual skin cells and will be injected directly into the patient's brains.

"It's much easier to commercialize in terms of manufacturing," said Ostrove, adding that it's also less risky.

If the study shows no safety concerns, the next test will be to show that the drug works. Ostrove said Positron Emission Tomography--PET scans--help reveal whether there is increased metabolic activity following treatment.

"Patients could have a single treatment and significantly slow their cognitive decline," Ostrove said.

But he expects it won't be until the end 2006 that Ceregene will report first results.

Ostrove hopes to raise up to $25 million in a second round of financing to fund the Alzheimer's study and a planned study testing a compound for Parkinson's disease.

South San Francisco-based Cell Genesys created Ceregene in January 2001 with $10 million in funding and intellectual property, and gene-therapy programs from Neurologic Gene Therapeutics, a San Diego-based company founded by UCSD scientists.