New Generation Alzheimer's Drugs: Do They Work?
Neuro Brain

We've all been hopeful that a new class of Alzheimer's drugs (monoclonal antibodies) would soon bring effective treatment to the growing number of Alzheimer's patients.

The latest approach is based on using antibodies that bind with harmful amyloid protein.  The idea is that the antibodies will be naturally flushed from the body by the immune system, and take the harmful amyloid away as well.

Major trials have now concluded on two such drugs: Bapineuzumab and Solanezumab.  The primary outcome measures of these trials were "improved cognition" and/or "improved function" versus a placebo group.  That is to say, if subjects who took these drugs had either better cognition or better physical ability to perform daily activities, compared to subjects who did not, then the drugs were probably effective enough to be approved by the FDA. On these measures, all trials have failed.

But that is not necessarily the end of the story for either drug.

A secondary analysis, performed on a combination of the data from the multiple Solanezumab trials, shows a small improvement in cognition among treated subjects.  It is a weak signal, but it provides some hope on which to build.  Especially noteworthy is that the positive effect was most evident in the earlier stage patients with healthier brains.

A stronger signal has come from a look at the targeted biomarkers (amyloid and tau proteins) that these drugs target.

Researchers have speculated (and common sense has suggested), that using such drugs to remove amyloid from the brains of subjects who have already suffered a fair amount of brain damage, may not be helpful.  The obvious experiment would be to remove the amyloid at an earlier stage, before brain damage occurs, which is before symptoms of memory loss and other cognitive decline are noted. This makes intuitive sense and is well-aligned with the possible effect detected in the Solanezumab trial on early stage subjects.

As such, a key indictor of the true potential for each drug may be actual measures of amyloid reduction in those subjects who were treated.  Researchers involved in the Bapineuzumab trial announced yesterday that the drug did in fact dramatically reduce amyloid in the brain and spinal fluid of trial subjects.  Similar biomarker data from the Solanezumab trial is expected in the coming weeks.

Overall, we wish that the drugs had produced great improvements in cognition and function.  While those goals were not met, it is encouraging to note that some, small measure of cognitive improvement may have been realized in the Solanezumab trials, and a clear reduction in amyloid protein was seen in the Bapineuzumab trials. 

This leaves us with a hopeful hypothesis that, if used on subjects at an earlier stage of Alzheimer's disease, before extensive brain damage has occurred,  either or both drugs may yield more effective treatment than what is currently available.

Contributed by: Dennis Fortier, President, Medical Care Corporation

To view the original Brain Today article, click here​.