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.
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.
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
Contributed by: Dennis Fortier, President, Medical Care Corporation
To view the original Brain Today article, click here.