New Alzheimer's studies show advances against different treatment targets

Two studies related to experimental Alzheimer's therapies reported positive results today at the 2008 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2008) in Chicago.

One Phase II trial, of a compound called AL-108, targeted early abnormal brain changes in a protein called "tau" in a condition related to Alzheimer's called mild cognitive impairment (MCI). The researchers saw improvement on various measures of memory. Another study examined brains of people with Alzheimer's half of whom had diabetes, and half did not. The researchers found that people in the study who took a combination of insulin and oral anti-diabetes medications had fewer Alzheimer's-related brain changes (amyloid plaques) than all the others in the study. This could be a pathway for developing new treatments.

Plus, a new study from the Mayo Clinic showed higher than expected rates of MCI in a large, older population. People with MCI have ongoing memory problems, but they do not have other losses such as confusion, attention problems, and difficulty with language. People with MCI are much more likely to get Alzheimer's than the general population.

"We are making progress. It is very important that we have as many drugs as possible in the pipeline for Alzheimer's, and that we explore every available avenue for treatments," said Ralph Nixon, MD, Ph.D., of the Alzheimer's Association's Medical and Scientific Advisory Council. "However, the population is aging, and we need to make significant advances soon in treatment and prevention of Alzheimer's or it will become an overwhelming epidemic, wiping out our healthcare resources and devastating Medicare."

Dr. Nixon is Professor of Psychiatry and Cell Biology, Vice Chairman of Research in the Department of Psychiatry, and Director of the Silberstein Institute at New York University School of Medicine. Dr. Nixon is also Director of Research and the Center for Dementia Research at the Nathan S. Kline Institute for Psychiatric Research.

Rates of Cognitive Impairment Higher Than Anticipated

As the field of Alzheimer's research moves toward earlier treatment and ultimately prevention, it becomes necessary to identify patients at the earliest point in the disease. Mild Cognitive Impairment (MCI) is the term used to describe the intermediate state between normal aging and the very earliest features of Alzheimer's, but its frequency in the population is not known.

Ronald C. Petersen, MD, Ph.D., and colleagues at Mayo Clinic, Rochester, MN, are conducting the Mayo Clinic Study of Aging, which is a longitudinal study of people ages 70 to 89 from Olmsted County, Minnesota. One of the goals of the Study is to follow healthy subjects over time to detect the earliest point of cognitive impairment. In 2004, the researchers recruited 1,786 people who were found to be cognitively normal, and reevaluated them a year later. All subjects underwent a baseline evaluation including an interview of the subject and their study partner by a nurse, a cognitive assessment, and a neurological exam by a physician.

Individuals in the study developed MCI at a rate of about 5.3 percent per year, and this rate was higher with advanced age - about 3.5 percent per year for 70-79 year olds and about 7.2 percent per year for 80-89 year olds. Men were nearly twice as likely to develop MCI as women.

"The rate of new MCI cases in this group was considerably higher than anticipated," Petersen said. "If we extrapolate Alzheimer's incidence rates to MCI, we would expect perhaps 1 to 2 percent per year, but our findings were substantially higher than that."

"These results underscore the urgency of developing new and better strategies to create disease modifying therapies for Alzheimer's. In addition, for public health purposes, we need to know how many people are cognitively impaired and potentially on the road to Alzheimer's," Petersen added.

AL-108 Trial (Phase IIa) Shows Promise of Tau-Targeted Therapies in MCI

MCI can be divided into two broad subtypes. Amnestic MCI (aMCI) significantly affects memory, while nonamnestic MCI does not. Other functions, such as language and attention span, may be impaired in either subtype. Persons with aMCI convert to Alzheimer's at a much higher rate than the normal aging population.

Donald Schmechel, MD, Adjunct Professor of Medicine (Geriatrics), Professor of Psychiatry, and Associate Professor of Neurobiology of Duke University Medical Center, Durham, NC, and colleagues conducted a Phase IIa clinical trial of AL-108 (Allon Therapeutics), an experimental therapy designed to combat neurofibrillary tangles (NFT). NFT are one of the early key abnormal brain changes in aMCI and Alzheimer's. AL-108 is a nasal spray formulation of an eight amino acid peptide, known as NAPVSIPQ, derived from the neuroprotective protein Activity-Dependent Neuroprotective Protein.