Mar. 6, 2003 UK scientists have made a major scientific advance by establishing proof of principle that the development of prion disease can be prevented in mice using monoclonal antibodies (mAbs). The work lays the foundation for further research to explore the potential of mAbs to treat specific prion diseases such as CJD and vCJD. The work is published today (6 March 2003) in Nature.
Mice in the 17 month study treated with mAbs remain clinically healthy almost a year after the untreated mice succumbed to the disease. Although the work is in its infancy and clinical studies with patients are some years away, the results raise the real possibility that mAb therapies might be effective against prion diseases.
Monoclonal antibodies are very versatile, forming the basis of many successful diagnostic tests, and an increasing number of therapeutic drugs. They are immune system molecules that bind very strongly to their target, in this case the prion protein.
A group of mice infected with scrapie prions (PrPSc) were given therapeutic doses of mAbs before they became ill with neurological signs of prion disease. The mAbs appear to have stopped the conversion of normal prion protein into the abnormal infectious form, preventing it accumulating. More importantly the mAb treatment appears to have delayed the onset of clinical disease indefinitely. The mice remain healthy.
A different group of mice were given mAbs for the first time once neurological symptoms of scrapie had developed and no therapeutic effect was seen. The mice later succumbed to the disease.
The work was funded by the Medical Research Council (MRC) with additional support from the Department of Health. The research team was led by Dr Simon Hawke at Imperial College London in collaboration with Professor John Collinge at the MRC Prion Unit at the Institute of Neurology and Professor David Anstee at the National Blood Service.
Research will now focus on achieving higher mAb concentrations in the brain when neurological symptoms and signs develop. Work will also be needed to 'humanise' the mAbs by genetically engineering them to more closely resemble human antibodies before they can be used for treating patients.
Dr Hawke said: "I'd like to urge caution about interpreting the results, as the work does not provide an immediate clinical preventative treatment or cure.
The work is a key scientific advance, but there is much more development work to be done before we can begin to think about translating this research to the clinic. The good news is we're making promising advances towards a possible treatment."
"On one hand, if future tests can identify those who are ill before neurological disease sets in, then mAbs might form the basis of a useful preventative treatment. Of course, the success of this strategy will depend on the availability of a reliable test to diagnose CJD in pre-symptomatic patients, which doesn't yet exist. On the other hand, if large enough concentrations of antibodies can be achieved in the brain, then treatment of patients with neurological disease might be possible, but we can't even begin to contemplate this until we've done work to humanise the antibodies. "
"By demonstrating that mAb technology could work for illnesses like CJD, we've made a promising start."
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