There is new evidence that we could develop an antibody to fight BSE, CJD and other diseases, writes Dick Ahlstrom
More evidence has emerged that suggests vaccination may help to defeat otherwise fatal diseases such as scrapie and mad cow disease. The work is also encouraging for researchers seeking a vaccine against Creutzfeldt-Jakob disease, or CJD, the human form of mad cow disease.
Dr Simon Hawke and colleagues at Imperial College London developed an antibody-based vaccine that blocked the progress of the disease in mice. Their results are published today in the journal Nature.
The diseases are part of a family known as spongiform encephalopathies. Invariably fatal, they are named after the sponge-like holes that develop in the brains of animals or people that develop the disease. The changes occur when a normal cellular protein called prion turns into an infectious form.
The normal prion is very short-lived in the body, but the aberrant form doesn't degrade, building up as plaques on brain tissues. High levels of the aberrant prion also accumulate in the spleen.
Scrapie, as the disease is called in sheep, has been known for hundreds of years, but great scientific interest was sparked in the 1980s, when cattle began to develop a similar disease, bovine spongiform encephalopathy, or BSE.
This interest quickly turned to alarm when a new human form of the disease emerged, later found to be associated with the consumption of BSE-infected meat. CJD is very rare; only one or two spontaneous cases occur here each year.
The arrival of variant CJD opened the appalling vista of hundreds or even thousands of BSE-related cases in humans, hence the urgency to develop a vaccine.
Elan, the troubled Irish pharmaceutical company, had a CJD vaccine in Phase II trials when the study was unexpectedly halted after some participants became ill. This vaccine, which is still under study, targeted the plaque build-up and in mice showed signs of reversing the disease and its symptoms.
The Imperial College group targeted the aberrant prions directly before they could begin to form plaques. They produced a vaccine that could knock out the infective form while leaving the normal prion untouched. The vaccine was used in scrapie-infected mice that had already begun to develop high levels of aberrant prions. There were accumulations in the spleen, but the mice had not yet developed clinical signs of the disease.
The results were striking. "We found that [aberrant prion\] levels and prion infectivity were markedly reduced, even when the antibodies were first administered at the point of near maximal accumulation of [aberrant prion\] in the spleen," the authors write.
The scrapie-infected mice remained healthy for more than 300 days after untreated animals had succumbed to the disease, the researchers found. "No clinical signs of scrapie or weight loss have yet been observed in these mice," they say. "Experiments are in progress to determine whether prion infection has been suppressed or eradicated in these animals and, if the latter, what period of treatment is required to effect a cure."
The study showed that normal prions remained untouched by the vaccine, allowing the researchers to assume that the vaccine inhibited aberrant prion production. They also pointed out, however, that the vaccine "had no effect late in the incubation period when clinical signs had developed". They also warned that unwanted side effects could arise using similar treatments in humans, although there was no sign of adverse effects in the mice.
"Despite these caveats, our findings are encouraging," the authors conclude. "These findings indicate that immunotherapeutic strategies for human prion diseases are worth pursuing."