Vol. 12 Issue 9 Page 8
New technology geared toward intervention
Researchers from the University of California, Los Angeles, (UCLA) have developed an innovative technique to image the onset of Alz.heimer’s disease in patients. By combining a chemical marker with positron emission tomography (PET), researchers have been able to detect the tangles and amyloid plaques indicative of the disease. The technique has implications for future medications and interventions, according to researchers.
This new technology was developed primarily by UCLA researchers Gary Small, MD, Parlow-Soloman Professor of Aging and professor of psychiatry and biobehavioral sciences, and Jorge R. Barrio, PhD, professor of medical and molecular pharmacology. Dr. Barrio developed the chemical marker FDDNP, which is injected into patients and attaches itself to the plaques and tangles. A PET scan then is performed that allows researchers to view where cell death has occurred in the brain.
Finding a molecule that could penetrate the blood-brain barrier was an obstacle that investigators had to overcome to continue their research, Dr. Small told ADVANCE. “The challenge was to find a molecule that would easily get into the brain. The .blood-brain barrier keeps compounds, molecules and chemicals in the bloodstream from getting into the brain. We needed a molecule that was small enough to get in but one that would be attracted to the plaques and tangles.”
Once the molecule was generated, a radioactive tag was added to it. When injected into a patient’s bloodstream, the molecule travels to the brain and attaches itself to the plaques and tangles. A PET scan measures the radioactive levels in different parts of the brain, allowing the researchers to determine where cell death occurs.
“We see the highest signal in the areas of the brain where we know the plaques and tangles are in the highest concentration,” Dr. Small stated.
Plaques and tangles are thought to disrupt cell function and kill off brain cells, resulting in disorientation and progressive memory loss in patients with Alzheimer’s.
The researchers also discovered that “the memory performance of people with relatively mild memory complaints correlates very well with the accumulation of the molecule in the memory centers of the brain,” he said.
Prior to the development of this technology, the plaques and tangles could only be identified when a patient was deceased. This is the first time that researchers have been able to identify the definitive hallmarks of Alzheimer’s disease in the living patient.
“Until now, the only way to see the physical evidence of Alzheimer’s was under the microscope at autopsy,” Dr. Small said. “We wanted to pinpoint Alzheimer’s in living subjects.”
The researchers originally tested the procedure on nine patients with Alz.heimer’s disease and seven control subjects. To verify their findings, a brain autopsy was performed on one patient who died during the study. Brain tissue from the autopsy revealed plaques and tangles stained by the FDDNP molecule, confirming the results from the patient’s prior PET scan.
In general, researchers have had success in using different forms of brain imaging, particularly PET scanning, to look at the function of the brain and to see patterns of abnormality in people in their 40s and 50s, according to Dr. Small.
Currently, one out of every 10 people over the age of 65 and nearly half of those over 85 has Alzheimer’s. By 2050 an estimated 14 million Americans will have developed the disease, according to the Alzheimer’s Association.
If this new technology proves to be an effective diagnostic tool, it will have worldwide implications for the millions of people at risk for the disease who might benefit from therapeutic interventions and medications.
The technique will speed up the search for more specific treatments for Alzheimer’s disease that will aim to prevent the accumulation of plaques and tangles or even clear them out of the brain after they’ve formed, Dr. Small said. “When we come to new treatments, it is going to be easier to protect brain cells before they are damaged than to repair damaged cells.”
In addition, this technology could reduce the amount of time and money required to develop new drugs for the disease.
“It costs a lot of time and money to discover a new treatment for any disease, whether it’s Alzheimer’s, heart disease or cancer,” he said. “One of the things that slows down the drug discovery is testing new drugs in hundreds and thousands of patients. If you have an accurate and effective marker for disease progression, that’s going to help you test these drugs in fewer patients so you can speed up the drug discovery.”
Ideally, this technology will become a widely available diagnostic tool that will give physicians the opportunity to detect the onset of Alzheimer’s in patients who are genetically at risk.
“There’s mounting evidence that the characteristic lesions of the disease begin many years, even decades, before people get the disease; so we want to identify that problem early on and intervene,” Dr. Small said.
The technique he has co-developed with Dr. Barrio will offer physicians that opportunity. Currently, it is being used solely as a research tool.
Prior to being made available in the United States, the technique will have to receive approval from the U.S. Food and Drug Administration (FDA). Before submitting the tool for FDA approval, the researchers hope to continue to improve the device at the most basic level and use it on a variety of individuals.
“We want to follow the natural course of the illness, look at other kinds of dementia, look at different age groups and normal people, and get a better idea of how well it works within each patient,” Dr. Small said.
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Nicole Klimas is assistant editor of ADVANCE.