阅读理解
Drug companies have spent billions of dollars searching for
therapies to reverse or significantly slow Alzheimer's disease, but in vain.
Some researchers argue that the best way to make progress is to create better
animal models for research, and several teams are now developing mice that more
closely imitate how the disease destroys people's brains.
The US National Institutes of Health (NIH), the UK Dementia
Research Institute and Jackson Laboratory (JAX) - one of the world's biggest
suppliers of lab mice - are among the groups trying to genetically design more
suitable mice. Scientists are also exploring the complex web of mutations(突变) that influences neurological (神经学的) decline in mice and people.
"We appreciate that the models we had were
insufficient. I think it's sort of at a critical moment right now." says
Bruce Lamb, a neuro-scientist at Indiana University ~ho directs the NIH-funded
programme.
Alzheimer's is marked by cognitive impairment(认知损伤) and the build-up of amyloid-protein
plaques (淀粉样蛋白块) in the brains of people, but the
disease does not occur naturally in mice. Scientists get around this by
studying mice that have been genetically modified to produce high levels of
human amyloid protein. These mice develop plaques in their brains, but they
still do not display the memory problems seen in people.
Many experimental drugs that have successfully removed
plaques from mouse brains have not lessened the symptoms of Alzheimer's disease
in people. One focused stumble came last month, when three companies reported
that their Alzheimer's drugs had failed in large, late-stage clinical trials.
Although the drugs successfully blocked the accumulation of amyloid protein in
mice, they seemed to worsen cognitive decline and brain shrinkage in people.
The drive for better mouse models comes as genomics studies
are linking the most common form of Alzheimer's to dozens of different genes.
This diversity suggests that each case of the disease is caused by a different
combination of genetic and environmental factors. "There is no single
Alzheimer's disease," says Gareth Howell, a neuro-scientist at Jackson
Laboratory (JAX) in Bar Harbor, Maine.
Howell argues that scientists' reliance on lab mice with
only a few genetically engineered mutations might have limited research. His
own work suggests that in mice, just as in people, genetic diversity plays a
part in determining how Alzheimer's develops.
