Developing drugs that effectively slow the course of Alzheimer’s disease has been notoriously difficult. Scientists and drug developers believe that a large part of the problem is that they are testing these drugs too late in the progression of the disease, when significant damage to the brain makes intervention much more difficult.
“Drugs like Lilly’s gamma secretase inhibitor failed because they were tested in the wrong group of patients,” says Sangram Sisodia, director of the Center for Molecular Neurobiology at the University of Chicago. People in the mid or late stages of the disease “are too far gone, there is nothing you can do.”
New brain imaging research may help solve that problem. Two studies presented at the Society for Neuroscience conference in San Diego this week identified changes in the brains of people who would go on to develop the disease. Researchers ultimately hope to use these changes to select patients for clinical tests of new drugs before they have developed signs of dementia.
“Brain changes that predict progression will hopefully allow us to detect the disease early, before it has caused irreversible damage,” said Sarah Madsen, a graduate student at the University of California, Los Angeles, at a press briefing at the conference.
Recent research has focused on people with a condition known as mild cognitive impairment, which involves memory loss and other cognitive problems and can be a precursor to Alzheimer’s. However, not everyone with this disorder will go on to develop the disease. A reliable method of predicting who will develop Alzheimer’s would enable drug developers to focus their clinical testing. By testing drugs only in this carefully selected group, drug makers could more easily see the potential benefit of an experimental drug. It would also help them to avoid unnecessarily subjecting people to health risks.
Sarah George, a graduate student at Rush University Medical Center, in Chicago, analyzed brain scans of 47 people with mild cognitive impairment, 22 of whom went on to develop Alzheimer’s over the next six years. She focused on a part of the brain called the substantia innominata, which is known to be severely affected in Alzheimer’s. Existing drugs for treating the disorder target a chemical messenger, acetylcholine, made by neurons in this part of the brain.
While George didn’t find differences in the volume of the substantia innominata between the two groups, she did find differences in the parts of the brain that those neurons connect to. People who went on to develop the disease had significant thinning in three connected areas of the cortex involved in memory, attention, and integration of sensor and motor information.