Headlines proclaiming the discovery of a potential Alzheimer's treatment are often in the news, yet a cure for the disease continues to elude scientists. So what's happening? Why do these seemingly promising studies fail to produce a reliable method of Alzheimer's prevention or treatment?
Take, for example, these headlines about the findings of some recent Alzheimer's studies:
- "Green Tea May Help Prevent Alzheimer's Disease"
- "New Alzheimer's Treatment Fully Restores Memory Function"
- "Alzheimer's Wonder Drug Can Stop Disease in its Tracks, Scientists Say"
Sounds promising, right?
But these headlines fail to explain one very important element of the experiments: who (or what) these therapies were tested on. In fact, each of these studies was conducted on mice, not men, a factor that makes a big difference in determining how a particular therapy will fare once human beings are brought into the experimental mix.
Mice have long been used in medical research because they are a boon for researchers. They're easy to breed and raise—so there's no shortage of test subjects—they can be infected with an array of diseases that also afflict human beings, and scientists have also discovered how to alter the genetic codes of mice to mimic certain human ailments.
There are a few drawbacks, however. Mice don't naturally develop Alzheimer's disease, so researchers have to work some behind-the-scenes genetic magic to make them suitable for testing.
How do you "give" a mouse Alzheimer's disease?
"You don't," says James Hendrix, Ph.D., director of global science initiatives for the Alzheimer's Association. "What you do is create a model of Alzheimer's disease." The mice are genetically modified so that they experience an abnormal accumulation of beta-amyloid protein and/or tau tangles in their brains—two hallmark biomarkers of Alzheimer's disease in humans. Scientists can then test different drugs and therapeutic interventions to see if they can reduce the amount of beta-amyloid or tau in the brains of the mice.
Let's take another look at those three studies:
- Green tea, exercise and Alzheimer's: Researchers from the University of Missouri used mice that had been bred to accumulate unnatural amounts of beta-amyloid in their brains, to see how running on a wheel and drinking water that had been infused with EGCG (compound found in green tea) impacted their cognitive functioning. By the end of the study, the mice who exercised and drank the enhanced water performed better on memory and cognitive functioning tasks, and the amount of amyloid in their brains markedly decreased.
- An Alz-blasting ultrasound: Scientists from the Queensland Brain Institute used a focused therapeutic ultrasound to break up beta-amyloid plaque deposits in the brains of genetically-modified mice. Seventy-five percent of the mice who were subjected to the ultrasound regained their full cognitive functioning, and none experienced damage to other parts of the brain due to the ultrasound.
- The latest wonder drug: Researchers from the University of California, San Diego developed a special protein that helped prevent the accumulation of beta-amyloid in genetically-altered mice. They also attained similar results after testing the effectiveness of the protein on human brain cells in the lab.
These results are undoubtedly promising and scientifically sound, but how well will they translate to human beings?
"This is a critical question and one that the scientific community has been dealing with for a long time," says Hendrix. "The mouse brain is obviously different than the human brain, and candidate drugs have gone into clinical trials with great fanfare, but then failed to show efficacy."
Mouse trials are extremely effective when it comes to studying infectious diseases, testing the safety of certain medications, and examining how drugs interact with other body processes. But Alzheimer's is such a complex ailment that scientists often have a hard time replicating rodent-based research results in human beings.
That's why it's important to take approach the conclusions of these mouse studies with the proper perspective. "We don't want to dim the enthusiasm for these studies," Hendrix remarks, "but we have to put them in the right context. Animal studies, by their nature, are still years away from producing a legal drug."
And so, we slowly inch closer to an eventual Alzheimer's cure, a journey that Hendrix argues could be sped up by increased funding for Alzheimer's research.
"The development of better animal models is an important area for funding," he says. "We know that we have these animal models, but we don't know if they're really getting to the core of the disease. With more research we think that we can get better models and therefore be more predictive."