A brief summary of important potential treatments and CAF’s related research.
There has been a lot of attention over the last several years about vaccines and Alzheimer’s disease (AD). The buildup of a protein in the brain, that our body normally produces, called “amyloid-beta” plays an important role in AD. The accumulation of amyloid-beta in the brain leads to ongoing nerve cell injury and this ultimately contributes to the cognitive decline we see in patients. It has been theorized that if one could prevent the buildup in the brain of amyloid-beta or could clear away what does build up, this could serve a treatment.
In 1999, it was shown that if mice that develop amyloid buildup in the brain were actively immunized with the amyloid-beta protein itself (amyloid-beta was injected under the skin of mice), they developed antibodies against amyloid-beta and had much less buildup in their brain. It was later shown, that if one directly infused antibodies against amyloid beta (called passive immunization) into mice, this would also decrease the buildup of amyloid-beta and in some cases, improve the cognitive deficits seen in the animals. Because of these exciting findings, many research groups began studies to better understand how active and passive immunization work and some companies moved ahead with clinical trials to see if these approaches might be useful to people.
Vaccine Trials in Humans
Soon after the realization of the potential therapeutic potential of active or passive immunization, Elan and Wyeth pharmaceuticals together began a trial in which amyloid-beta was directly administered to humans subcutaneously (active immunization). Over 300 patients were entered into these trials in the US and Europe. It was noted that ~ 6% of the patients developed a potentially serious complication called acute encephalitis (confusion with variable neurological deficits associated with inflammation in the brain). This trial was then halted. Interestingly, the complication did not seem to be due to antibodies generated against amyloid-beta, but another type of inflammation induced by the treatment. Several of the patients from this trial have died for other reasons and interestingly, most have evidence that a large amount of amyloid was cleared from the brain. Further, while the trial was aborted, there is also evidence that memory has not worsened as much in those people that developed antibodies to amyloid-beta.
The field continues to move forward in this area. Because passive immunization (direct administration of anti-amyloid antibodies) should not, in theory, have the same complications as active immunization, companies such as Elan/Wyeth, Lilly, and others have started human trials to see if infusion of these type of antibodies can have beneficial effects. Results from these trials should emerge in the next 2 years. In addition, some companies are also starting active immunization trials again with modified versions of amyloid-beta that they believe will not have the same side effects.
How is Cure Alzheimer’s Fund Involved?
There are at 3 researchers funded by CAF that are collaborating on work related to immunization and AD. Drs. Virginia Lee, Charles Glabe, and David Holtzman are all exploring the detailed role of specific forms of the amyloid-beta protein called oligomers. They are looking at whether particular antibodies targeting amyloid-beta can tell us more about the cause of AD and new ways for treatment. Coupling findings from this new research, with new discoveries from the laboratory of Dr. Rudy Tanzi on genetic risk factors for AD, should allow us to begin treatment for AD much earlier than is currently possible. The bottom line is that there is good reason to believe these approaches have significant potential as treatments in the future. However, it’s critical for future studies to figure out how to best clear amyloid from the brain without inducing serious side effects.
David Holtzman, MD
Professor and Chair of Neurology