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Parkinson's patients desperate for help sign on to hole-in-the-head study Sam Whiting Sunday, April 22, 2007 Randy Calvert isn't sure if he got the 16 drops of Parkinson's Disease treatment on his brain or not. But he's sure he got the twin holes drilled into the front of his skull. That's the gamble in a randomized controlled study. Calvert, 54, was willing to "bet the house" that he is among the 66 percent who got a brain injection of an experimental gene therapy product in a study at UCSF Medical Center. "Yesterday I woke up knowing I had the juice because I had a symptom-free day," he says. As he talks, his head is rolling on his neck, his shoulders and arms moving every which way. "Symptom-free day," he allows, "may be an exaggeration." Calvert is among 51 Parkinson's patients nationwide taking part in a Phase 2 study of CERE-120, which has shown potential to treat the symptoms "characterized by muscular tremor, slowing of movement, partial facial paralysis, peculiarity of gait and posture, and weakness," according to Stedman's Medical Dictionary. The disease causes a loss of dopamine, the lubricant for the central nervous system. Drinkers and smokers spend their lives trying to trick the brain into releasing more dopamine, so to lose what comes naturally is devastating. "It's all about hope and desperation," Calvert says. "You've got to be pretty desperate if you're letting them cut into your brain." In Phase 1, recently completed, 12 patients were given the treatment and averaged a 40 percent improvement in motor skills, according to the principal investigator Dr. William Marks, associate professor of neurology at UCSF. This was enough to convince the Michael J. Fox Foundation for Parkinson's Research to grant $1.9 million for Phase 2, after giving $740,000 to Phase 1. The Phase 2 study will cost more than $10 million. "Current treatments only control the symptoms," Marks says. "The hope is that this gene therapy might also slow down or stabilize the disease." CERE-120 was developed by Ceregene Inc., a private San Diego biotech concern that was founded in 2001 as a subsidiary of Cell Genesys Inc. of South San Francisco. To confirm the effect of CERE-120, all 51 volunteers have submitted to the one-time surgery, which takes five hours. For people who drew the sham surgery, the holes go only halfway through the skull. Calvert awoke to "a helluva headache for three or four days." But he doesn't know if his holes went all the way through. Neither does Marks, 41, or his colleague in the study, Dr. Jill Ostrem, 37, assistant professor of neurology and co-investigator. Only the drillers, neurosurgeons Philip Starr and Paul Larson, know who got the treatment, and neither is actively involved in evaluating the patients' outcomes. CERE-120 is an engineered biological compound consisting of the DNA shell of a virus, into which codes for the growth factor neurturin have been inserted. "In Parkinson's disease, brain cells that control movement gradually die," Marks says. "Bathing these dying cells in neurturin may help them to stay alive and functioning." The liquid formula is applied by long needle, four injections on each side of the brain. Then the holes in the skull are sealed by titanium caps and closed. There is no known cause or cure for Parkinson's, which typically affects people older than 55. Calvert, an energy engineer, got hit when he was 46 at a dinner party at his home near Sacramento. Seated at the head of the table, he reached for his knife to cut his steak and couldn't lift it. That was his first symptom of Parkinson's, though he'd had foot cramps for two years -- a Parkinson's hint known as dystonia. Medication is the first line of treatment. The herky jerky movements common to Parkinson's patients are a side effect of the drugs, usually levodopa. When the medicine is working, the muscles are loose and the movement indicates the brain is responding. Over time, levodopa loses its effectiveness and you have to keep increasing the dosage. Calvert takes a pill every three hours, including at night. When it wears off, he stiffens up and can't sleep, and when awake he can barely move and has no balance. Four months ago he came to UCSF to pursue the second line of treatment -- deep brain stimulation, which involves implanting probes on either side of the brain to give an electric pulse. He was told about the CERE-120 study, talked to two of the 12 patients in Phase 1 and was persuaded. Either way he'd have to have to have his skull opened, but as he reasoned, "I'd rather go the non-hardware route than have two electrodes in my brain and a battery pack in my chest." UCSF is the only California hospital participating in the trial, and Calvert was the third patient to enter it. Every few months he comes in for tests including blood work, X-ray, MRI, psychological exam and motor and cognitive skills tests. It will be a year before he learns whether he got the dose of CERE-120. If it works, the people who got the placebo will be given the option to undergo a second surgery. The titanium caps just have to be popped off, and the holes extended through the skull so CERE-120 can be applied. All participants are asked to report to UCSF for testing once a year for life. They are also asked to submit to a postmortem exam. "On top of everything else," Calvert says with a laugh, "they throw in a free autopsy." E-mail Sam Whiting at swhiting@ sfchronicle.com. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn