Wherever he is buried in the body, illness leaves traces in the blood, or so the thinking goes. But finding these biomarkers, which can help catch the disease early on, was a futile exercise, with a promising candidate after another lose its luster once it receives scrutiny. A team of chemists and other researchers now offer a new way to pick up the biomarkers with a blood test: the detection of antibodies the body makes in response to specific diseases. So far, the group has reported results for only a small number of patients with Alzheimer's disease. But they hope the approach will and could be used for everything from lupus to cancer.
There are two common strategies to find biomarkers in blood or elsewhere in the body. The first is to focus on what is known about a disease for example, looking for the deterioration of certain areas of the brain in Alzheimer's disease. The second is essentially a fishing expedition in which researchers compare, for example, protein patterns from patients who have a particular disease with patterns of people who do not. Both methods have encountered roadblocks. In the case of Alzheimer's disease, PET, MRI, spinal taps and remove some of the fluid that surrounds the brain and spinal cord have had some success in the early diagnosis, but they are expensive or invasive. Although there is no cure for Alzheimer's disease, researchers are eager to find easy to use and reliable biomarkers, which would ensure that people in clinical trials of Alzheimer's disease really have the disease and make early treatment possible if it eventually becomes available.
chemist Thomas Kodadek of the Scripps Research Institute in Jupiter, Florida, and his then-postdoc, M. Muralidhar Reddy, considered biomarkers that exploit a classic feature of the biology of the disease: antibodies, proteins that the immune system churns in the presence of invaders. Scientists do not know that each disease causes antibodies, but certainly some diseases do. "Antibodies are proteins rocks the world," not easily damaged when studied in the laboratory, said Kodadek. This has made the idea of measuring the blood attractive.
Many other researchers have examined the value of antibodies as biomarkers, but they were thwarted by the common strategy used to test for them. To know which antibodies to search, you need to determine what molecules stimulate the immune system to produce antibodies. This requires "a phenomenal understanding of the progression of the disease early," said Kodadek, something we do not have for most diseases.
Kodadek, Reddy and colleagues took a different approach . They have turned to "libraries" of thousands of peptoids, molecules that are developed in drugs that have a myriad different structures. the idea was that some peptoids, by chance, would bind to all that the antibodies could be there even a few thousands of randomly selected shoes could fit your feet-allowing researchers to determine whether people with a disease had an abundance of certain antibodies that healthy people were missing. at mice with a version of multiple sclerosis, a library of 4,0 peptoid identified three antibodies, the team used to diagnose the disease in other mice.
Six people with Alzheimer's disease, the same strategy, using 15,000 peptoids, picked up two antibodies found at high levels. The antibodies are also abundant in the blood of an additional 16 Alzheimer's patients. But these were rare proteins in the blood of a handful of people with the disease or lupus Parkinson.
The antibodies are also prevalent in two of 16 healthy controls. Their presence may indicate that the biological markers are not specific to Alzheimer's disease. Or it might suggest that these two women, aged 75 and 65, have early Alzheimer's disease. "We support this hypothesis, but it can not be concluded with certainty," the authors report in the January 7 issue of cell .
"There is a new idea," says Norman Relkin, a neurologist and neuroscientist at Weill Cornell Medical College in New York. "You are looking for immune responses that may be specific to the disease." However, Relkin said that for Alzheimer's disease at least, it will take much more work to do reliable test, especially because even with healthy aging, "the immune system tends to produce antibodies more dysfunctional."
Although the results need to be replicated and more people to ensure that the antibodies are specific to Alzheimer's disease, the paper "looks like a very thorough job," says Kaj Blennow, neurochemist to Sahlgrenska university hospital in Gothenburg, Sweden. a blood test would have great advantages over current Alzheimer's diagnosis, he says
Kodadek, Reddy, and others formed a company, Opko Health Inc. to further develop the technology. Reddy is the Chief scientific Officer. "as you can tell, I'm pretty excited about it," said Kodadek. But he tries to keep his enthusiasm in check. "There is a long history of biomarkers hit the cemetery," and although he is hopeful that will not happen here, "the point is, you never know."
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