WASHINGTON, DC—“A cure for Alzheimer’s (AD) has not been found on my watch, but the momentum is there,” said Marcelle Morrison-Bogorad, PhD, at what might be her last opportunity to speak before Congress as the director of the National Institute on Aging’s neuroscience division. Morrison-Bogorad announced her intention to retire this year at a hearing of the House Energy and Commerce Health subcommittee. She admitted she was leaving her post—one she has held since 1996—at a time when there are no definitive answers regarding the prevention and treatment of AD, but where there are a number of promising research paths.
Desperately Seeking Biomarkers
The last five years have been especially turbulent in the field of AD research at NIA. An Alzheimer’s summit in 2006, followed by a 2010 state of the science conference, and any number of specialized workshops have provided NIA with numerous recommendations for how to proceed in its research efforts.
The 2010 conference was especially enlightening, when AD experts disclosed that there was no evidence so far that any effective behavioral interventions for AD exist. “It was determined that we ought to devote more resources to these questions,” Morrison-Bogorad said. “And even before that report was finalized, we’d stepped up our funding of clinical trials to get definitive evidence of whether or not exercise and clinical interventions could impact age-related cognitive decline, cognitive impairment, and AD.” Currently NIA is funding 20 such trials.
However, the area of greatest promise and greatest need in AD research is the identification of biological and imaging markers for AD and other cognitive disease. Such markers would allow better monitoring of AD in clinical trials, as well as help identify people at risk for the disease preclinically. “We do think that understanding the earlier stages of AD is very important. When NIA reissued its request for research applications eight years ago, we said, ‘Forget about late stages of disease. We want you to really concentrate on the earlier stages,’” Morrison-Bogorad said. “One of the things that has held us up is not being able to identify preclinical stages.”
One of the most promising projects in this field is the Alzheimer’s Neuroimaging Initiative (ADNI), which is testing whether PET, MRI, and other scanning technology can be combined with biomarkers and clinical assessments to provide a better measure of the progression of cognitive disease. “This is especially useful in people who are not yet showing symptoms or people who are developing mild cognitive impairment,” Morrison-Bogorad said.
ADNI researchers have already established a method for testing the levels of AD’s characteristic tau and beta-amyloid proteins in cerebral-spinal fluid, and have correlated those proteins with changes in cognition over time. “This is possibly the most amazing breakthrough in the last several years,” Morrison-Bogorad said. “We now see that 20% of older adults have amyloid plaques in their brain that are equivalent to someone with AD, even though they are functioning normally.”
These preclinical stages will be essential to understanding the course of the disease if techniques for prevention and treatment are to be discovered.
Another key is the growth of investigational drug development. NIH has over 60 projects working to bring new AD drugs to the stage of FDA approval for clinical trials. Strong NIH support into the beginnings of the drug discovery process is needed because pharmaceutical companies are often unwilling to invest resources at this stage. Research into new drugs is needed, since the ones that have been tried to date have been ineffective.
“One reason that drug trials have not worked so far may be that the drugs are given too late in the disease to have any effect,” Morrison-Bogorad said. “But prevention trials to test those possibilities take a lot of money and time under current protocols.”
One way that NIA has managed to get around this cost is by attaching cognitive measure protocols to clinical trials looking at other conditions. However, some AD therapies are directed against unique aspects of the disease, for which specialized interventions are needed, and for which there are no research short-cuts. The only answer is for NIA to fund more AD-specific trials.
“We make difficult decisions all the time about where to put our resources. We do not have a crystal ball to tell us what approach will eventually pay off and relieve suffering from this frightening disease. We are committed to trying every promising avenue. And we will succeed.”