Mouse models for neurological disease

An article in the prestigious science journal Nature has decried the use of mice as “models” for testing drugs intended for use in humans as “nearly useless”.

Three major potential new drugs for Alzheimer’s Disease tested on mouse “models” of the disease have failed in the last year alone. Although scientists can create mice with brains that contain “plaques” (characteristic deformities) resembling those seen in the brains of Alzheimer’s patients, the mice do not have dementia, and drugs that targeted these plaques have repeatedly failed in human trials. This is leading scientists to question whether the mice truly mimic what happens in the human brain.

Furthermore, almost a dozen drugs that helped mice with amyotrophic lateral sclerosis (ALS), a progressive, usually fatal disease of the nerves, to live longer have failed to aid humans. In fact,

“In the most recent and spectacular of these failures, [a drug] which had seemed modestly effective in four separate ALS mouse studies since 2002, was found last year to have worsened symptoms in a clinical trial of more than 400 patients.”

The author goes on to point out that there are no good mouse models for Parkinson’s Disease, and even the mouse model for Huntingdon’s Disease, which has  a simple genetic cause, does not suffer from all the same symptoms. This shows yet again how recreating even a seemingly straightforward genetic fault in another species cannot be relied upon to mimic the human condition, because the background biology of each species is just too different and complex.

The article ends by questioning whether researchers will be willing to accept that mouse models are not only difficult and expensive to use, but don’t predict results in humans. Quoting clinical neurologist Michael Benatar, who works at Emory University School of Medicine in the US:

“I think there’s a sense of desperation that we need a convenient model for bringing drugs to clinical trial”…But desperation, he adds, is an inadequate justification for the continued use of a poor model.

“It’s a bit like the proverbial drunk who keeps looking for his lost keys under the lamp post, simply because the light’s better there.”

Standard Model: Questions raised about the use of ‘ALS mice’ are prompting a broad reappraisal of the way that drugs are tested in animal models of  neurodegenerative disease. Jim Schnabel, Nature, Vol 454,682-685. (a subscription is required to access the article)

(the use of italics in the quotes is ours)

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