News from the International Conference on Alzheimer's Disease

Two recently completed studies are grounds for "cautious optimism" in the treatment of Alzheimer's disease during its earliest stages.

In one study, a Phase II clinical trial jointly funded by the US National Institutes of Health and Singapore-headquartered TauRX Therapeutics, the investigational drug methylthioninium chloride (MTC; brand name Rember) was shown to have significantly slowed the progression of early and mild cases of Alzheimer's.

The results demonstrated that, in a group of 321 patients that were divided into 4 groups that received either a low; a midrange, a high dose of MTC or an inert placebo, the midrange dose was more effective in preventing the decline in performance on widely-used psychological tests used to measure reasoning and memory impairments that are characteristic of Alzheimer's disease.

The study, reported by neurobiologist Claud Wischik of Aberdeen University, found that those treated with MTC showed either very little or no change in their test scores after as much as 19 months of follow-up versus an average decline of 7% in the low dose or placebo groups. The treatment group also showed improvement on brain scans that measure overall function in those areas that are most closely associated with memory and decision-making

MTC appears to work by dissolving what are known as "tau protein tangles," which are now known to be "framework" on which the more familiar beta-amyloid plaques eventually form. Beta amyloid plaques destroy the portions of brain cells known as dendrites where it is believed that both long and short term memory is processed and stored.

Another report described the early results of treatment with a drug that inhibits the formation of beta amyloid by a different pathway, by interfering with the interaction of beta amyloid with the trace elements zinc and copper.

The study found that the drug, known as PBT2, not only reduced the amounts of other proteins found in elevated amounts in the blood and spinal fluid of Alzheimer's patients but also appeared to improve scores on the psychological tests that measure decision-making and short term memory. PBT2 was also shown not to cause adverse reactions such as nausea, vomiting, or other conditions that would cause the drug to be withdrawn during treatment.

Other studies were focused on the problem of detecting Alzheimer's disease in its earliest stages, before the symptoms of the disease, such as memory loss and confusion, appear.

It has long been known that the amounts of certain classes of proteins present in the spinal fluid can predict the occurrence of Alzheimer's with accuracies approaching 80%. However, since testing for these substances involves a spinal tap to obtain the amount of fluid necessary for a complete "profile," the tests are not routinely used as a screening examination.

A team of researches assembled by Avid Pharmaceuticals reported that a Phase II trial has demonstrated that positron emission tomography (PET) scans utilizing a compound known as AV-45could become the first widely available examination used to detect Alzheimer's in its earliest stages, even before symptoms of the disease appear.

AV-45 is known to bind itself to beta amyloid which, in patients without symptoms of Alzheimer's disease, is normally present in only small amounts that are uniformly distributed throughout the brain. Studies with this compound consistently demonstrated abnormal concentrations of beta amyloid in those parts of the brain that are known to be the first sites damaged by the disease.

The study did not attempt to evaluate the predictive value, meaning its ability to identify those that would eventually develop Alzheimer's, but rather proved that AV-45 is both reliable and safe to administer in clinical practice. Further, more extensive, studies on its value as a diagnostic test and as a method for monitoring the results of different treatments are planned for the near future.

There are currently an estimated 4.5 million cases of Alzheimer's disease in the United States.

The results from all studies mentioned above were presented this week at the International Conference on Alzheimer's Disease 2008 in Chicago.