In many diseases, proteins get modified. When that happens, the immune system should notice those modified disease proteins (or antigens), mark them as foreign and mount a response.
If antibodies – molecules in blood that stick to the antigens – are specific to a disease, it makes sense that a lot of them should be found in those with the disease (and not in healthy people). And a test that could recognize those antigens or the antibodies against them could help diagnose diseases early. But what if you don’t know what the antigens or antibodies are?
"In Alzheimer's, or in a disease such as cancer, it's not at all obvious what the initiating event is," says Thomas Kodadek of Scripps Research Institute. "We just don't know what are those first weirdly modified proteins that are unique to the disease process that the immune system 'sees.'"
There are two common strategies for finding biomarkers in the blood or elsewhere in the body. The first is to focus on what's known about a disease – for example, looking for deterioration in certain brain regions in Alzheimer's disease. The second is essentially a fishing expedition, in which researchers compare, say, protein patterns from patients who have a particular disease with patterns from people who don't have it.
According to a new study, the antibodies could be used to recognize other kinds of molecules. Molecules that can then be used to screen for antibodies found in the bloodstream of people with specific diseases (and not in healthy controls).
Kodadek's team created glass slides coated with thousands of differently shaped, randomly selected, unnatural molecules known as ‘peptoids’ – which “are really just random shapes," explains Kodadek.
Then the team bombarded blood samples from people with Alzheimer’s with thousands of peptoids, with hopes of fishing out disease-specific antibodies – or signatures of the disease in the bloodstream.
They identified three peptoids that recognized antibodies from people suspected to have the disease. They tested these against 16 people who actually have Alzheimer’s, and each peptoid proved more than 93% accurate at diagnosing Alzheimer's.
The team has since applied the test to about 300 people, correctly diagnosing 98%, according to Kodadek.
Currently, the only way to conclusively distinguish Alzheimer's from other dementias is by examining the gnarled plaques and tangles of protein found in the brains of those with the condition. This can only be done after death. A furious search is under way for earlier, less-invasive tests using brain scans, blood draws and spinal taps, for instance.
Globally, over 35 million people suffer from Alzheimer's. There are no effective treatments for the disease or proven means of preventing it.
"If this works in Alzheimer's disease, it suggests it is a pretty general platform that may work for a lot of different diseases," Kodadek says.
But would an early test for Alzheimer's disease be useful today given that there aren't any real treatment options? This kind of test might be most useful to pharmaceutical companies, by allowing them to better identify patients with early Alzheimer's for enrollment into clinical trials.
“It’s unclear whether people would want to know a couple of years ahead of time they are going to get Alzheimer’s if they can’t do anything about it,” Kodadek says. “But I can say with some certainty that we will never get a good therapy for Alzheimer’s without early diagnosis.”
If those antibodies and the natural antigens that they recognize could be found using the new technology, it might even aid the development of new and more effective cancer vaccines designed to bolster the body's natural defenses against the disease. “The dream scenario," Kodadek calls it.
The research was published in Cell last week.
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