By R.L. Fielding
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 Aß antibodies.
To accomplish this they created an oral vaccine that attached Aß DNA to an
adeno-associated virus vector, which served to mitigate T-cell activation. Thus
they were able to decrease Aß levels in the brains of the mice and yet not
activate T-cells to the degree they had before, greatly reducing the risk of
meningoencephalitis.
In the other new study, conducted at the University of Illinois at Chicago,
researchers succeeded in making the passive immunity protocol much safer. This
they accomplished by changing the point of entry for the Aß antibodies. Rather
than injecting the antibodies into the body of the mice, as was done previously,
antibody was injected directly into the brain of the mice. Because the
antibodies were injected directly into the brain, smaller doses were needed, and
side effects were minimized.
The results of the above studies, and the potential for further optimized
immunization strategies may prove to be watershed events in the history of
Alzheimer's treatment.
Covance is a leading provider of innovative antibody products and custom
antibody development services to the research community for Alzheimer's disease.
Visit www.Covance.com for more in-depth information and to view the suite of
products for Alzheimer's disease. Boris Predovich is Vice President of
Immunology and Surgical Services at Covance Research Products.
Notes
1. J.A. Hardy, G.A. Higgins (1992), Science, 256:184-5.
2. M.P. Lambert et
al (1998), Proc Natl Acad Sci, 95:6448-53.
3. D.M. Walsh et al (2002),
Nature, 416:535-9.
4. Neelima B. Chauhan et al (2004), Journal of
Neuroscience Research, 78, 5:732-741.
Hideo Hara et al (2004), Journal of
Alzheimer's Disease, 6, 5:483-488.
R. L. Fielding writes on many health-related topics.
Article Source: http://EzineArticles.com/
