UCSD Grafts Genetically Altered Cells Into Rats
Researchers at UC San Diego have successfully grafted genetically altered cells into the brains of rats with symptoms similar to Parkinson’s disease, generating a “significant” reduction in abnormal behavior associated with the disease, according to the authors of an article to be published today in a professional journal.
The research, described in the current issue of the Proceedings of the National Academy of Science, is the latest in a series of projects that suggest that genetically modified cells might one day be used to treat human disorders.
The research being conducted by UCSD professors Theodore Friedmann, a medical doctor, and Fred Gage, a neuroscientist, marked the first time that scientists have observed a behavioral effect that was generated by a genetically modified cell implanted in a research animal’s brain.
The implanted cells, called fibroblasts, were genetically modified to produce L-dopa, a chemical that is deficient in the brains of patients suffering from Parkinson’s disease. Oral administration of L-dopa typically reduces certain symptoms of Parkinson’s disease in rats and humans.
After two weeks, the rats that received L-dopa-producing cells exhibited a significant reduction in a behavior associated with Parkinson’s disease. Rats that received unmodified cells showed no improvement, leading researchers to believe that the grafted cells were producing L-dopa in amounts that had a direct impact on the rats’ behavior.
UCSD’s research demonstrates “that the ability to combine transplantation techniques with gene transfer is potentially a powerful approach to the treatment of human central nervous dysfunction,” according to the article.
The modified cells were implanted in specific portions of the brains of rats that are known to have a neurological condition that mimics symptoms of Parkinson’s disease. Because of that neurological condition, the rats constantly walk in circles. That “rotational behavior” was reduced by 40% in rats that received the L-dopa-producing cells.
The use of cell grafts to treat Parkinson’s disease has “received a lot of attention” in recent months, said Friedmann, a member of UCSD’s Center for Molecular Genetics. However, the surgical grafting of adrenal tissue into the brains of humans with Parkinson’s disease has produced controversial results, Friedmann said.
However, UCSD’s continuing project “is conceptually different” from past research because cells are modified to produce L-dopa before being implanted in brain tissue, Friedmann said.
Previous research conducted elsewhere has shown that certain symptoms of Parkinson’s disease can be reversed through the implantation of fetal brain tissues. But federal law now prohibits researchers from using fetal tissues for transplants, and Gage believes his research offers “a possible alternative” for researchers who are hamstrung by federal regulations.
Although not as effective as fetal tissue transplants--the UCSD research generated just a 40% recovery rate after two weeks--it is “feasible that we can improve the ability of the cells to produce (L-dopa) and stimulate further recovery,” Gage said.
Gage cautioned that it will be years before research can be directed toward humans. “It is still real early on,” Gage said. “We’ve got lots of more work in rodents to improve the ability of cells to make this product.” Researchers also must learn how to regulate production of L-dopa in the modified cells, as well as prove that L-dopa production, and resulting gains, hold up for longer than two weeks.
In related research described last December, Gage and Friedmann successfully implanted genetically altered cells into rats’ brains in order to prevent further deterioration of brain cells that otherwise would have died.
Gage described the most recent research results as an “important and encouraging step” in the effort to create genetically modified cells that can treat disease by producing chemicals in the brain.
“We’re interested in basic science that will lead to generic approaches to various brain disorders,” Gage said. He described the research as being “potentially applicable” to a number of diseases.
