Transfer Tactic
by Adam Istas
July 2007
A novel technology platform may hold the potential to significantly advance the treatment of neurodegenerative disorders.
Major advances in biotechnology and a greater understanding of the physiological effects of medicine have opened the door to entirely new concepts of therapies for many diseases. From alternative delivery systems to novel recombinant-engineered proteins, the treatment options for a number of conditions continue to grow at an impressive pace. As with traditional, small-molecule drug development, the process of shepherding a biologic therapeutic through clinical development is wrought with uncertainty and requires start-up companies to operate under a unique business model.
Aside from two major medical breakthroughs for the treatment of symptoms associated with Parkinson’s disease—the introductions of Levadopa and deep brain stimulation (DBS)—there is no approved medical therapy for patients afflicted with the progressive neurodegenerative disorder. But the search for a cure and for an acceptable treatment for the debilitating symptoms continues in earnest, due in part to a greater public awareness and newer biotechnology processes that make the impossible seem attainable.
“Because there’s so much more knowledge about the disease, there’s a tremendous improvement in the treatment of people with Parkinson’s disease,” says Jose Garcia-Pedrosa, president and CEO of the National Parkinson Foundation (NPF), in Miami, Fla., USA. In addition, Garcia-Pedrosa cites better pharmacokinetic knowledge as having a tremendous impact on the way Parkinson’s patients are managed medically. “There are now ways to compensate for the side effects of medications that we didn’t have before,” he says.
According to Garcia-Pedrosa, the NPF promotes the use and development of therapies that dramatically improve the quality of life for Parkinson’s patients. NPF provides funds for research into the underlying cause of the disorder, and also funds programs that better assist patients and their caregivers in managing the condition. “Even though the state of the science has increased exponentially, we really don’t know when the cause and cure will be found,” Garcia-Pedrosa says. But a new gene delivery technology in the early clinical phases of development may help alleviate the symptoms of Parkinson’s and it also may be shown to be effective in halting its progression.
Deliver the Gene
Ceregene is a five-year-old biotechnology company in San Diego, Calif., USA that is focused specifically on neurotrophic factors to treat neurodegenerative diseases, including Parkinson’s. “Neurotrophic factors have captured the imagination of medical scientists for decades,” says Raymond Bartus, Ph.D., senior vice president of clinical and preclinical research and development at Ceregene. “They hold extremely powerful potential for restoring dying and degenerating neurons and protecting them from further damage,” he says.
Although other researchers and companies have attempted to use neurotrophic factors for neurodegenerative purposes, all of the previous efforts have failed. “It’s not that the biology has been wrong, but getting the factors to the targeted area has proven to be very difficult, if not impossible, because they’re very bulky,” Bartus says. In recognition of this delivery problem, Ceregene developed its novel gene transfer technology as a possible way to exploit the tremendous value of neurotrophic factors. The concept behind gene transfer is quite simple, he says. “Rather than trying to deliver the protein, you simply deliver the gene and have the gene be expressed where it’s needed.”
Results from an open-label, Phase I trial of CERE-120, Ceregene’s leading candidate for Parkinson’s treatment, were encouraging. The two-site study included 12 Parkinson’s patients who underwent stereotactic neurosurgery to receive a viral vector engineered to express the neurotrophic factor, neurturin, directly into the putamen. Long-term follow-up data presented in April 2007 indicated a 36 percent reduction in Parkinson’s symptoms at 12 months. Bartus is quick to point out the results are preliminary in that the study was open-label, but he adds that Ceregene elected to move quickly into a multi-site, double-blind, controlled study (which includes a sham surgery) to determine conclusively that the technology works as well as the early findings suggest.
Another advantage of gene transfer is that the process involves a single treatment. “We have our own evidence that our products continue expressing on a constant basis for well over two years,” Bartus says. “Basically, people in the field believe that it’s lifetime expression. As long as the cell is alive, the protein will keep expressing.”
Although the Phase I trial of CERE-120 was not powered statistically to determine if the treatment was effective in slowing down the progression of Parkinson’s, Bartus says that it’s certainly possible. “The biology of these growth factors is such that if we are getting a genuine reduction in symptoms, their biology would predict clearly that we should also slow down the rate of progression,” he says. “It’s hard to imagine neurturin doing one without doing the other.”
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