May 26, 2000 (Washington) -- In April 1989, Joseph Sardo of Miami, Fla., was assigned to a new project. Soon afterward, he became withdrawn. At first, his family blamed it on the project. But by June, the data process administrator who once was able to add columns of 30 numbers in his head, could not even count back from seven. By August, he was dead at age 66.
Sardo suffered from Creutzfeldt-Jakob Disease, or CJD, a rare brain disorder characterized by sponge-like microscopic spaces in the nerve cells, called neurons, that cause progressive dementia and muscle spasms. It is thought to afflict about one person in 1 million. It can strike anyone, there is no treatment, it cannot be slowed, and it usually is fatal within one year.
Approximately 10 to 15% of CJD cases are inherited, yet how Sardo and the others contracted the disease remains unknown, which worries U.S. health officials. However, with a new, more infectious variation of CJD, better known as "mad cow disease," now posing an additional threat, they are taking no chances. In early June, FDA officials will once again meet with an "ad hoc" advisory committee created in 1995 to discuss what would be an appropriate response.
On the agenda is a blood donor deferral policy that has been credited in part with creating a national blood shortage, and the merits of a method that might free up that blood for transfusions as well as the manufacture of plasma derivatives. Adopted in August 1999, the deferral policy bans the use of blood donated from people who spent six or more months in the U.K. between January 1980 and December 1996.
The stakes could be high. Mistakes have been made in the past with regards to CJD and other infectious diseases. Between 1963 and 1985, the National Institutes of Health (NIH) supplied free of charge a human growth hormone that infected some recipients with CJD. And in the 1980s, the failure of government officials to form an appropriate blood donor policy with regards to HIV/AIDS literally led to an epidemic, during which thousands of Americans were infected while regulatory officials wrestled with the question of how to respond.
In this case, there are some striking similarities. "We simply don't know if there is the potential for CJD to be in the blood of donors," explains Steve Petteway, director of pathogen safety and research at Bayer Corp., where groundbreaking work has been done on that subject. But studies have shown that the infectious agent may reside in the blood of animals, which lends credibility to the FDA's concern, he says.
To find the answer, scientists around the world are working on a test to detect an unconventional protein called a prion, a previously unknown infectious agent believed to be behind CJD. Prions are thought to transform healthy molecules to a dangerous conformation, causing not only CJD but also mink encephalopathy, scarpie in goats and sheep, chronic wasting disease of mule deer and elk, feline spongiform encephalopathy, and bovine spongiform encephalopathy -- or mad cow disease.
Experiments with mice in which scientists managed to transfer CJD using prions show there is good reason to believe that prions are the cause of the disease, says Mary Jo Schmerr, PhD, the lead scientist for prion diseases at the National Animal Disease Center, a division of the USDA.
Based on that data, Schmerr has developed a test for animals and is now working on a test to extract prions from concentrated human blood samples. Such a test, she tells WebMD, would go along way toward detecting the disease in its early stages, when treatment might still be possible.
Based on that data, others also are working on a test to confirm whether their methods for extracting matter from the lining of the human brain and for extracting blood components reduces the risk of inadvertently transferring the disease from an infected person to a healthy person. So far, that work has demonstrated the value of using animal models, and that once the prions are removed, the disease cannot be transferred, Petteway tells WebMD.
But at least one researcher who has studied CJD for 25 years still is disputing the official version of what causes CJD, and if he is right, researchers may not be able to develop a reliable early screening test. Also at question is whether government regulators can accurately assess the risk posed by CJD, which some say may be far more prevalent than originally thought.
It is entirely possible that bacteria may be the cause of CJD, says Frank Bastian, MD, a professor of neuropathology at the University of South Alabama. Although prions appear in people with the disease, Bastian believes that prions are a product rather than a cause of the disease. There are bacteria that fit the criteria, he tells WebMD. Moreover, there is no actual proof that prions are the cause, Bastian says.
Bastian became interested in this explanation when he discovered during a brain biopsy a microorganism that reminded him of spiroplasma, he says. Unlike prions, spiroplasma contain both RNA and DNA, and in many ways fit a number of criteria for the type of agent that could cause an infectious disease such CJD, Bastian tells WebMD.
Prions may be an accurate marker, but without further research, there is a chance that these prion-based diagnostic tests may miss less virulent forms of the disease, Bastian says. "We simply have to do more research because we don't know the full spectrum, and we don't have a diagnostic test," he tells WebMD. "We could be looking at the tip of the iceberg."
But while scientists agree that there is no direct proof that prions cause CJD, the NIH still refuses to fund Bastian's research. "They just say it's all solved. It's the prion," he tells WebMD. Worst of all, he says, the NIH appears to be "throwing all their eggs into one basket when it would make more sense to spread out the research."
The NIH could not be reached for comment at the time this story was written. However, there is now overwhelming support for the prion theory, says Joseph Berger, MD, chair of neurology at the University of Kentucky.
"I don't think it's debatable," he tells WebMD. Prions are the only possible explanation for a disease that is both inherited and infectious, he says.
Cecile Sardo is Joseph Sardo's surviving wife. After Joseph died, Cecile helped found the Creutzfeldt-Jakob Disease Foundation to help other surviving family members get through the experience. For her, the important thing is that CJD finally is moving to the forefront of federal regulators' attention, she says.
"I remember the lonely feeling. You feel like an alien," she tells WebMD, referring to the lack of community support that existed when her husband died.
- Researchers are working out the basics of what causes the rare brain disorder called Creutzfeldt-Jakob Disease (CJD) and its severe sibling, "mad cow disease."
- Initial studies point to a protein called a prion, which may be causing the characteristic sponge-like brain damage and may even be able to be passed between people. In other cases, the disease seemed to be inherited.
- Doctors aren't sure if the disease can be spread through a blood transfusion, but CJD has been spread through human growth hormone treatments. In June, the FDA will decide what should be done to try to control the disease.