As scientists make new prion discovery, antiprion technologies hit home and abroad
BY STEVE SMITH
WASHINGTON, DC-National Institutes of Health (NIH; www.nih.gov) scientists have recently discovered that prion proteins become toxic when they latch on to the outside of cell membranes, and if a method can be found to break the fatty bond, effective treatments for such prion-induced diseases as human mad cow disease could be forthcoming.
Although researchers at the NIH’s Rocky Mountain Laboratories are still trying to determine what exactly makes the rogue proteins poisonous to brain cells, they have determined that when enough prions accumulate, they deposit plaque that eventually leads to dead brain cells.
Meanwhile, American companies continue to make inroads in prion-removal advances, both in the United Kingdom, where mad cow disease has been most intense, and at home.
In the U.K., variant Cruetzfeldt-Jakob (vCJD) prions, which lead to human mad cow disease, are being attacked through Pall Corp.’s Leukotrap Affinity prion reduction filter system, which removes the deadly prions from blood transfusions. Variant CJD is transmitted by eating contaminated beef and can be transmitted by a contaminated blood transfusion. Those who may be infected with the disease can be asymptomatic for up to sixteen years, so attacking the prions at the blood-transfusion level is crucial in such countries as the United Kingdom, where 155 of the 172 cases of vCJD reported since 1994 have occurred.
Last month, the Council of Europe “marked” the Pall technology for meeting pan-European essential requirements for medical device safety. In the coming months, Pall says, the prion-reduction filter will be evaluated by the U.K.’s National Blood Service and the Irish Blood Transfusion Service, with results expected as early as the end of this year.
The Leukotrap filter technology is designed to remove all types of prions from red blood cells, at 99.9 percent efficiency. Since filtration is already a part of standard blood processing and handling in the U.K. and other European countries, Pall says its solution will be more cost-effective than other methods such as pathogen inactivation, which relies on chemical additives.
“We are working very closely with health authorities, starting with the nations hardest hit by vCJD, to help protect the safety of the blood supply and prevent the spread of this disease,” says Pall Corp. Chairman Eric Krasnoff.
The company continues to develop technologies that will meet specific health requirements of other European nations, followed by Canada and the United States.
STERIS Corp. (www.steris.com), which has introduced its Hamo 100 PID antiprion detergent in the U.K., says its low-foaming alkaline technology for clean-in-place systems and automated washers used for cleaning surgical instruments is proving effective at several U.K. health facilities.
“We have had a number of hospitals conduct cleaning trials and have successfully shown a significant decrease in the rejection rates-the number of devices that are returned for cleaning-which is an excellent example of the practical use of the [Hamo 100] product,” says Dr. Gerald McDonnell, senior director/technical affairs at STERIS Ltd. in Basingstoke, U.K. “We have also had great interest in the technology in France and Germany.”
The STERIS detergent’s documented antiprion effectiveness had originally been at a 1.6 percent dilution in water, at 43°C for 15 minutes, but according to Dr. McDonnell, “Subsequent work has shown that the product is effective over a range of temperatures, concentrations and exposure times, thereby allowing for more flexible applications-including lower concentrations and contact times.”
Testing detergents for antiprion effectiveness is vital, says Dr. McDonnell, since some cleaning chemistries, including alkaline-based cleaners at the same pH test with Hamo 100, “have shown little to no ability” to decontaminate prions on the surfaces of surgical instruments or pharmaceutical manufacturing surfaces.
“Some alkaline and enzymatic cleaners have actually been shown to increase the risk by making prions more resistant,” Dr. McDonnell continues. “This highlights the importance of testing products and claims in standardized surface tests, as we described in our Lancet paper last year (See: The Lancet, Vol. 364, Issue 9433, August 7, 2004; www.thelancet.com).
In the U.S., STERIS says it continues to work closely with the Environmental Protection Agency (EPA) and Food and Drug Administration (FDA) to establish its CIP-100 technology as an acknowledged antiprion cleaning solution. “We have had limited claims and applications approved in certain states with another STERIS product, based on the same test methods and data,” says Dr. McDonnell.
In other U.S.-based antiprion efforts, Pall says it is developing an ante mortem test to detect infectious prions in cattle prior to entering the food supply. That technology, the company says, is in the “research stage.”
Meanwhile, LipidViro Tech Inc. (www.lipidviro.com), a Salt Lake City development-stage biotech company, has submitted research scheduled to be presented at this month’s Meeting of the International Union of Microbiological Societies in San Francisco, demonstrating that its proprietary ozone-based technology reduces prion infection in bovine serum below the limits of detection in both cell and Western Blot assays-said to be the “gold standards” for prion detection.
“These are the first scientific results that demonstrate an ability to inactivate infectious prions while maintaining a fluid’s biological integrity,” says LipidViro CEO Ken Hamik. “Producing prion-free bovine sera for the biopharmaceutical industry will help safeguard many widely used vaccines and drugs from potentially transmitting infectious prions.”
LipidViro’s findings are based on two proprietary pieces of equipment that produce and deliver a standardized dose of ozone. A DPD (Drug Production and Delivery) system produces a precise, measured dose of ozone that helps to accurately target the threshold that produces prion inactivation while maintaining the biological integrity of the fluid. A GFE (Gas-Fluid Exchange) device then mixes ozone with the fluid, a process that LipidViro claims significantly improves the ability to inactivate prions and is the only one to deliver precise, measured doses of ozone that are “consistent and reproducible.”
Speaking to concerns that blood from those infected with vCJD could transmit the deadly prions via transfusion, Hamik says, “We will be investigating our proprietary process to inactivate infectious prions in human blood-derived fluids as well.” III