Prion disease treatable if caught early

The researchers said that their findings support developing early treatments that aim to reduce levels of prion protein in the brains of people with prion disease. Also, they said that their findings suggest testing the efficacy of treatments in a new way: by analyzing their cognitive effects in prion-infected mice.

The researchers, Giovanna Mallucci and colleagues, reported their findings in the February 1, 2007 issue of the journal Neuron, published by Cell Press.

Prion disease—such as the version of Creutzfeldt-Jakob disease believed to be contracted from cattle with “mad cow disease”—is caused by aberrant, infective proteins. It has been thought that the disease is untreatable.

However, in previous studies with prion-infected mice, Mallucci and colleagues found that early brain degeneration can be reversed if prions are depleted in neurons.

In the new studies published in Neuron, they established that cognitive and behavioral impairments—which appear early in humans with prion disease—can be reversed if prion depletion is done early. What’s more, they found that the neurological pathology of the disease is reversed along with the cognitive and behavioral deficits.

In their studies, the researchers measured the effects of prion disease on the animals’ ability to discriminate novel objects in their cage and on normal burrowing behavior. In both cases, deficits in those abilities appeared early in the disease. Also, studies of the animals’ brain tissue revealed a parallel impairment of signaling among brain cells.

However, when the researchers manipulated the animals to deplete their brains of the prion protein, their memory ability and burrowing behavior recovered. Importantly, found the researchers, the signaling among brain cells also recovered.

“Overall, we conclude that the dramatic benefits to neuronal function and survival in prion-infected mice we have shown here support targeting neuronal [prion protein] directly as a therapeutic approach,” wrote Mallucci and colleagues.

“Our findings of early reversible neurophysiological and cognitive deficits occurring prior to neuronal loss open new avenues in the prion field,” they wrote. “To date, prion infection in mice has conventionally been diagnosed when motor deficits reflect advanced neurodegeneration. Now the identification of earlier dysfunction helps direct the study of mechanisms of neurotoxicity and therapies to earlier stages of disease, when rescue is still possible.

“Eventually it may also enable preclinical testing of therapeutic strategies through cognitive endpoints. These data now lead to the hope that early intervention in human prion disease will not only halt clinical progression but allow reversal of early behavioral and cognitive abnormalities,” wrote the scientists.