Engineered human progenitor brain stem cells are able to produce and deliver into the brain a growth factor that shows promise in treating Parkinson's disease, say researchers at the University of Wisconsin-Madison.
A major challenge in treating Parkinson's and other neurodegenerative brain disorders is getting drugs to the desired areas of the brain. The brain's structure effectively blocks the delivery of most drugs via the bloodstream. The engineered progenitor brain cells are designed to sneak drugs past the blood-brain barrier.
The University of Wisconsin team obtained and grew large numbers of progenitor cells from human fetal brain tissue and engineered those cells to produce the growth factor called glial cell line-derived neurotrophic factor (GDNF).
Some small clinical trials showed that GDNF provide relief from the debilitating symptoms of Parkinson's disease. However, GDNF could not cross the blood-brain barrier and had to be pumped directly into the brains of Parkinson's patients in order to work.
In this latest study, researchers transplanted the engineered progenitor cells into the brains of rats and monkeys. The cells effectively integrated into the brains of the animals and delivered GDNF to the targeted brain areas.
The findings were published in the Dec. 15 issue of the journal Gene Therapy.
"This work shows that stem cells can be used as drug delivery vehicles in the brain," University of Wisconsin-Madison neuroscientist Clive Svendson said in a prepared statement.
More information
We Move has more about Parkinson's disease.
According to the EPA, seven of the eight violations in the lawsuit involved DuPont's failure over the past two decades to report important data on perfluorooctanic acid (PFOA) -- a breakdown product of "fluorotelomer" compounds that include the Teflon brand of non-stick chemicals.
"This is the largest civil administrative penalty EPA has ever obtained under any environmental statute," Granta Nakayama, EPA's assistant administrator in the Office of Enforcement and Compliance Assurance, said at a press conference Wednesday afternoon. "The settlement sends a clear message to the regulatory community that EPA takes very seriously the requirement to submit substantial risk information about toxic chemicals."
The EPA settlement mandates that DuPont pay a $10.25 million penalty and another $6.25 million to support two EPA environmental projects, including a $5 million, three-year look at the "degradation potential" of nine of DuPont's fluorotelomer-based products to break down and form PFOA.
In a statement, Dupont noted that "the settlement closes this matter for DuPont without any admission of liability."
A second statement from DuPont senior vice president and general counsel Stacey Mobley said, "We have already cut PFOA emissions from U.S. plant sites by 98 percent, and we are committed to reducing those emissions by 99 percent by 2007."
Susan Hazen, principal deputy assistant administrator in the EPA's Office of Prevention -- Pesticides and Toxic Substances, told reporters that the jury is still out on the health effects -- if any -- of PFOA in humans.
"The agency has information based on animal studies and toxic effects in animals, [but] we have no information at this point that would lead us to believe there is a significant human health impact," she told reporters, adding that EPA-funded studies looking at PFOA's impact on human health are ongoing.
But Lauren Sucher, director of public affairs for the Washington, D.C.-based nonprofit Environmental Working Group, said that research suggests PFOA collects over time in the bloodstream and takes decades to eliminate.
"There are also studies showing harm to workers, including an increased risk of leukemia, and workers with higher cholesterol levels, which is clearly a risk factor for heart disease," Sucher said.
PFOA accumulates in the blood over time. Although the EPA has not yet labeled PFOA a human health hazard, prior studies have linked the compound to increased risks for leukemia and high cholesterol.
"Whistleblower" testimony earlier this year from Glenn Evers, a former long-time DuPont scientist, also bolstered the case that the company had withheld data for years on risks posed by PFOA.
According to a recent ABC News report, DuPont officials "strongly dispute" Evers' claims, which they labeled "personal opinions that are inaccurate."
Because of their fire-, grease- and water-repellant properties, fluorotelomers have been ubiquitous for decades in products such as Gore-Tex fabric, upholstery, carpeting, paper food containers and "Teflon" non-stick cookware.
The Environmental Working Group filed a petition with the EPA more than two years ago claiming a DuPont cover-up, which in turn helped prompt the agency's lawsuit against the company.
"We're very satisfied that the EPA acted on our petition and actually sued DuPont for covering up vital health and safety information for over two decades," Sucher told HealthDay.
But she pointed out that, under existing rules, the agency could have levied fines of up to $313 million. Even that amount would be just a fraction of the billions of dollars in revenue DuPont has made from its Teflon-related products, she said.
"Given that DuPont has profited from illegal cover-ups over the past two decades, would the maximum fine have been more satisfying and a stronger deterrent? Sure," she added.
According to Nakayama, the eight counts cited against DuPont in the EPA suit included:
- failure to submit data from 1981 on the trans-placental movement of PFOA in humans,
- failure to submit data on PFOA levels in household drinking water,
- failure to reply to an EPA request for PFOA toxicity data,
- failures to submit information on elevated PFOA levels in the blood of residents living near DuPont's Washington, W. Va. Plant;
- data withheld from PFOA-related rat studies.
Nakayama said the first count was considered the most serious.
"This is the first and only information about human placental transfer and levels of PFOA in children," he said. "Human data is very rare, and information concerning PFOA in children, much less the fetus, is extremely rare and significant in researching the potential developmental effects of the chemical."
So where does all this leave consumers, who every day touch, and dine from, products containing fluorotelomer chemicals that may degrade to form PFOA?
"It's something consumers should be concerned about, but not alarmed by," Sucher said. "We'd suggest, though, that consumers definitely take opportunities to minimize exposure to these chemicals."
Those "opportunities," she added, include staying away from Teflon cookware; microwaving take-out food on a plate rather in the potentially PFOA-emitting container it came in; avoiding water- and stain-repellant clothing; and foregoing those special "stain-guard" coatings the next time you buy a carpet or sofa.
More information
For more on PFOAs, visit the U.S. Environmental Protection Agency .
Comment by Chi Van Dang, MD, PhD
