A critical turning point is coming for Ceregene by the end of the year. The San Diego-based biotech company expects to get results in the next couple months on whether its experimental gene therapy can effectively help treat Parkinson’s disease.
I got the overview of what this is all about a few weeks ago during a visit to the lab of Mark Tuszynski, a neuroscience professor at the University of California, San Diego, and Ceregene’s founder. He’s awaiting results of a trial that will have big implications for the much-maligned field of gene therapy, and for patients with Parkinson’s, who haven’t had a new advance to cheer about in decades. This could also be important news for Cambridge, MA-based Genzyme (NASDAQ: GENZ), which signed a partnership last year with Ceregene to get rights to this drug outside of North America.
Parkinson’s, a degenerative disease of the central nervous system, robs patients of their ability to control movement and speech. It is usually treated with generic L-dopa, which helps replenish the brain’s diminishing supply of dopamine, according to the National Institutes of Health. About 1.5 million people in the U.S. have the disease, which lasts for years, according to the National Parkinson Foundation.
Ceregene’s unusual idea is to use a single shot loaded with genetically modified viruses, called AAV, that shuttle copies of genes into the brain. Once the genes get there, they will churn out growth factor proteins that could prevent cell death in the brains of Parkinson’s patients, Tuszynski says. Biotech’s biggest companies, Amgen and Genentech, haven’t been able to get their proteins to do their thing with other delivery methods, so this could represent an important advance for Parkinson’s patients and gene therapy, he says.
“This is a one-time procedure in a patient’s lifetime, that hypothetically could confer years of neuroprotection,” Tuszynski says.
The drug, called CERE-120, works this way. It delivers a gene for neurturin, a natural brain protein that can repair damaged and dying dopamine-secreting neurons, Tuszynski says. Getting that protein to the right spot is part of the trick. The procedure involves drilling a small hole in the skull to deliver the gene that has the code for neurturin deep into the brain, but not throughout the rest of the body, Tuszynski says. The virus has shown in more than 90 patients that it is safe, and doesn’t cause inflammation or any worrisome side effects, he says. The theory is that once the protein gets in the brain, it will be constantly expressed, meaning that it will provide ongoing protection to nerve cells and won’t require repeat dosing, the way L-dopa does, he says.
Gene therapy, of course, is known for being intensely hyped. A 1994 cover story in Time— “Genetics. The future is now”—crowed that “new breakthroughs can cure diseases and save lives.” The technology fascinated people by using tiny modified viruses to shuttle human genes into cells, where the genes could correct genetic malfunctions at the roots of disease. Then the field crashed in controversy in 1999 after an Arizona teenager named Jesse Gelsinger died in a gene therapy trial at the University of Pennsylvania.
Ceregene missed out on that trouble, having been founded in 2001, after the Gelsinger controversy. Even today, none of the basic gene therapy research has advanced far enough to mature into a marketed product for sale by the FDA.
“We have come a long way since the early days of gene therapy, and have learned from the mishaps of previous years,” Tuszynski says. “It took 20 years to realize the benefits of monoclonal antibody to treat human disease, and I believe that we are near a similar milestone in the field of gene therapy,” he adds
Years of animal tests show that the gene therapy is able to continually express the protein where it belongs in the brain for at least six years, according to one study at the University of California, San Francisco, Tuszynski says.
Both of Ceregene’s clinical trials of this drug were partly paid for by the Michael J. Fox Foundation, led by the actor who suffers from Parkinson’s. The company has also raised $69 million in venture capital through its history, from Alta Partners, MPM Capital, Investor Growth Capital, Hamilton Bioventures, California Technology Ventures, and South San Francisco-based Cell Genesys (NASDAQ: CEGE).
Ceregene’s first Parkinson’s trial, which looked at two different doses and involved 12 patients, found a 35 percent improvement in symptoms one year after the procedure, Tuszynski says. Nine of the 12 patients had what were considered clinically meaningful responses. Of those who responded, the average improvement in symptoms was 52 percent at the longest time of follow-up, which was two years for patients on a low dose, and 18 months on a high dose, Ceregene has said. By three months, researchers saw improvement, and that benefit was sustained, Tuszynski says. The higher dose was found to be safe and more effective, so that’s the one Ceregene chose to advance to the next stage.
The next trial, an even more meaningful event, is a Phase II study that will produce results by the end of the year. It enrolled 58 patients, with two-thirds of them getting the CERE-120, and one-third in a control group who got a sham surgery. An independent board of safety monitors hasn’t found any adverse events that would cause researchers to stop the trial, Tuszynski says. The big question will be how well it works after one year, compared with the sham procedure.
Whatever happens, the outcome will have significant ramifications for the field of gene therapy, and for Parkinson’s research. “People in the gene therapy field are well aware of this program. There’s also a buzz out there on Ceregene in the investment community,” Tuszynski says.
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