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Tom Kodadek

Towards An Early Diagnosis of Alzheimer’s Disease

Although scientists now understand a lot about the mechanism of Alzheimer’s disease (AD) at a basic level, these insights have yet to be translated into effective therapies.

Scripps Florida’s Tom Kodadek, vice chair of the Department of Chemistry, believes the major stumbling block is the absence of an inexpensive and effective blood test to pick up the disease in its early stages.

“I am often asked why we are so focused on developing an early AD diagnostic,” he said. “Since there is no approved drug for it, why would you want know? But it is extremely difficult to develop an effective drug in the absence of early detection.”

Dr. Kodadek points out several studies have shown the degeneration and death of neurons that eventually leads to AD is under way for at least 20 years before symptoms appear, at which point the patient’s brain has sustained massive damage.

“The irony is we may already have in hand potential drugs capable of reducing neurological damage,” said Dr. Kodadek. “But clinical trials are doomed to fail because these drugs are designed to slow the rate of neurodegeneration. With a test to identify patients early on, a clinical trial could determine the efficacy of such a drug in slowing or stopping progression of the disease.”

The snag in early detection to date has been that researchers have failed to identify molecules in the blood tightly linked to AD progression.

Dr. Kodadek and his colleagues, however, have hypothesized the immune system reacts to AD and, as part of that response, produces unique antibodies (antigens) directed against AD-specific molecules not present in a healthy person. If true, then a blood test monitoring these molecules would allow detection at a presymptomatic stage.

“When we first suggested this, many people thought we were a little nuts because of two big problems,” he said. “One is that there was no hard evidence that there is an immune reaction to AD. The second is that, even if there were, we have no idea what the antigens might be to measure their levels.”

To address these questions, Kodadek and colleagues developed a radical new approach. They created a collection of millions of different chemical compounds of varying shapes, sizes and properties and then exposed them to the circulating antibodies in healthy individuals or people with AD. By comparing the results, they were able to identify chemicals that bound to antibodies present in the blood of AD patients, but not healthy volunteers. These promising preliminary results were published in 2011.

Since then, the scientists have found in larger-scale trials that more work will be needed for their findings to become a clinically useful tool.

“We are going to have to put in more effort to either optimizing the anti-body-binding chemicals and/or discovering improved probes,” said Dr. Kodadek. “We are exploring both of these avenues now. I am optimistic that this approach will eventually provide us with a good diagnostic for AD. Moreover, the work opens up a raft of possibilities in other areas, especially the early diagnosis of cancers and autoimmune diseases, which could have a huge clinical impact.”

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kodadek
Professor Tom Kodadek is working on early detection of Alzheimer’s, which he hopes will open the door to a host of new therapies.