— A novel treatment can rescue the brain function of mice afflicted with a form of mad cow disease, a new study suggests.
Researchers say that blocking the production of certain proteins completely reverses the memory loss caused by the illness. But they stress that adapting the approach to work in humans diagnosed with the equivalent illness, variant Creutzfeldt-Jakob disease (vCJD) will take many years.
Animals and humans naturally produce normal prion proteins in the nervous system. However, abnormal prions that are misfolded can disrupt normal prions. This disruption causes healthy prions to misfold too, leading to mad cow disease or, in its human form, vCJD. The result is brain damage, characterised by a lack of coordination, dementia, and ultimately death.
Giovanna Mallucci at University College London in the UK and colleagues used mice genetically engineered to stop producing normal prion proteins at around 10 weeks of age the equivalent of about age 25 in humans. They also used a control group of normal mice.
At one-week-old, both groups were infected with misfolded prions, and all began showing the typical signs of prion illness, including mental decline: tests revealed the mice all had impaired memory.
The control mice continued to show a consistent decline in memory. But, starting at nine weeks of age, the genetically altered mice began showing memory improvements in the tests. In fact, they regained a normal capacity to recall objects, says Mallucci.
It is the first study to demonstrate that the mental impairments including memory loss caused by prion disease may be reversed.
Mallucci believes the genetically engineered, or transgenic, mice recovered from the illness because they stopped producing prion proteins. As a result, there were fewer normal prions for the misfolded prions to disrupt.
Window of opportunity
Previous experiments have shown that mice lacking prions altogether cannot become infected with prion disease, Mallucci says. Blocking prion production can extend the life of transgenic mice infected with this illness, studies have shown.
The new findings should give people hope that a cure for prion disease may one day be found. It actually suggests that there may be a window of time in which one could intervene and treat vCJD, says Howard Federoff at the University of Rochester School of Medicine in New York, US.
But Mallucci cautions that switching off the production of prion protein in humans presents a great challenge. You can rescue brain function in mice [with the new approach] but its a long way away from being a treatment that works in people, she explains. In the future, scientists might create a drug to block prion production or design a gene therapy treatment to do the same.
Federoff also notes that while the mice have reached early adulthood at nine weeks of age, the animals brain development continues for at least another three weeks. This could explain how they recovered memory in Malluccis experiment and casts some doubt on whether blocking prion production could achieve the same recovery later in adulthood.
There is also some concern that stopping prion production could slow nerve growth, as normal prions appear to encourage this process (see When prions are good for the brain here).
Encouragingly, Malluccis study found no difference in brain cell growth between the experimental and control mice.
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Journal reference: Neuron (DOI: 10.1016/j.neuron.2007.01.005)