New Hope for Alzheimer's Treatment
There is now widespread agreement among research scientists and
medical professionals that Alzheimer's Disease (AD) is a problem
quickly growing to vast proportions. As the life expectancy of
Americans continues to rise, increasing the percentage of the
population over 65 years of age, so does the number of
Alzheimer's cases.
It is currently estimated that people over 65 years of age have
a 10% chance of developing Alzheimer's, while those over 85 have
a 50% likelihood of developing AD, making it the leading cause
of dementia among older people. Though the disease is associated
primarily with memory loss, its effects also comprise a number
of other severe disabilities, including changes in personality,
disorientation, difficulty with speech and comprehension, and a
lack of ability to move normally.
Consequently, most Alzheimer's patients require a great deal of
care, costing society close to $100 billion annually. According
to Christian Fritze, Ph.D., Director of the Antibody Products
Division at Covance Research Products, "The impact of
Alzheimer's Disease on our society will only increase as our
population ages. The prevalence of the disease and disabling
effects on the patient are significant by themselves. In
addition we are becoming increasingly aware of the far-reaching
effects on families, care-giver networks and the economics of
our health care system. The drive for progress towards effective
treatments by the research and drug development community is
growing stronger every day."
A New Consensus
But recent developments in the medical research community do
provide some hope. During the last two years, there has been a
growing consensus among Alzheimer researchers about the cause of
Alzheimer's disease, providing focus for scientists exploring
the new treatment options.
The focus is on amyloid beta oligomers, a new wrinkle on an
older hypothesis called the "amyloid cascade hypothesis".
Widespread acceptance of this new conclusion is something of a
milestone in the history of Alzheimer's research. As Dr. Fritze
says, "The decades old quest for the causative agent in
Alzheimer's Disease has recently focused on the precursors of
amyloid plaques. These precursors are part of a bewildering
array of processed (APP) Amyloid Precursor Protein) variants,
Tau isoforms and secretase components that play a role in
neuronal cytotoxicity and subsequent brain dysfunction."
Amyloid plaques are sticky protein deposits in the brain
containing amyloid beta peptide. Researchers have associated the
buildup of this plaque with Alzheimer's disease since its
discovery in 1907. But despite the clear correlation, scientists
were not sure what, exactly, spurred the onset of Alzheimer's
Disease. The hypothesis that amyloid beta accumulation in the
brain is the major cause of Alzheimer's Disease1 has been the
focus of much attention over the past decade. Although this
hypothesis was the leading explanation for the cause of AD, it
had several weaknesses. The most obvious problem with the theory
was the fact that the buildup of amyloid beta peptides did not
necessarily correspond with the severity of Alzheimer's
symptoms.
However, in 19982 and in 20023, researchers proposed that it was
not the amyloid beta plaques themselves that were neurotoxic -
and therefore the cause of Alzheimer's - but rather precursors
to amyloid beta plaques formed by smaller aggregates of amyloid
beta. These new ideas are gaining widespread acceptance among
the Alzheimer's research community, creating a consensus that
had not existed before.
This new focus provides one more spur to action for Alzheimer's
researchers, and underscores the need for further advancement.
"The AD field demands sophisticated, highly-sensitive research
tools to track these components and quantitate the existence of
monomeric, oligomeric and fibrillar amyloid forms present in the
progression of Alzheimer's disease," says Dr. Fritze.
Antibody Treatment
Two new studies, both released in October 20044, suggest that
new treatment options may be on the horizon. The studies are the
modification of one of two previous attempts using amyloid beta
(Aβ) antibodies in the treatment of Alzheimer's Disease.
The previous attempts, though not successful, did at least
suggest new courses of action in Alzheimer's research and
provided invaluable information for researchers.
In the first of the two previous attempts, researchers injected
the antigen itself - pieces of the beta amyloid protein that
makes up amyloid plaque - into mice, in the hopes that the
injections would generate an immune (antibody) response against
amyloid. Results were initially positive. The injected antigen
produced Aβ antibodies and slowed the onset of the disease
by decreasing Aβ levels. However, when tried on humans, the
procedure led to meningoencephalitis (an inflammation of tissue
around the brain) in some patients, and was therefore halted.
In the second attempt, a passive immunity therapy was tried in
which antibodies to amyloid beta (not amyloid protein) were
injected into mice, but hemorrhaging and inflammation ensued due
to the high antibody doses required to be effective.
New Hope
But now there appears to be new hope for the use of antibodies
as therapeutic agents for the treatment of Alzheimer's patients.
In the first of the two new studies that appeared in October
conducted by the National Institute for Longevity Sciences,
NCGG, and the Center for Neurological Diseases, Brigham &
Women's College, Harvard Institute of Medicine, researchers
modified the first procedure. Concluding that the
meningoenchaphalitis which occurred in some patients was caused
by autoimmune T-cell activation, the researchers hoped to
develop a vaccine that could minimize this T-cell activation
while retaining the production of A