Eukarion, Inc
http://www.eukarion.com/
Life span extension and prevention of neurological deterioration in mice
demonstrated with synthetic catalytic anti-oxidants
Studies support potential new approach to treating Parkinson's, Alzheimer's
and
other neurodegenerative diseases
Novato, CA and Bedford, MA, November 1, 2001 - Neurodegenerative diseases such
as Parkinson's and Alzheimer's disease may be attenuated through the use of
certain drugs, known as synthetic catalytic scavengers of reactive oxygen
species (SCSs), that powerfully augment natural anti-oxidant systems,
scientists reported in the November 2001 issue of the Journal of Neuroscience.
The report details experiments in which treatment with SCSs rescued a severe
neurological phenotype in mice engineered to undergo a specific form of
oxidative damage. Treatment with the SCSs also resulted in a dramatic
enhancement of lifespan of the mice.
The research contained in the report was conducted through a collaboration
among scientists at the Buck Institute for Age Research (Novato, CA),
Eukarion,
Inc. (Bedford, MA) and others.
The studies utilized mice that lack a form of superoxide dismutase (SOD2), a
natural anti-oxidant enzyme found in the mitochondria. The mitochondria
essentially serve as the powerplant of the cell, utilizing oxygen and
nutrients
to generate the energy that is critical to cellular functions. As a byproduct
to this key process, known as oxidative metabolism, the mitochondria also
produce potentially damaging reactive oxygen species and, hence, the
mitochondria's own antioxidant defenses are extremely important. Oxidative
damage to the mitochondria has been implicated in several neurodegenerative
diseases and disorders, including Parkinson's and Alzheimer's diseases,
amyotropic lateral sclerosis (ALS), Freidrich's ataxia, and aging.
Previous studies showed that mice lacking SOD2 undergo oxidative damage to the
mitochondria and, concomitantly, suffer a variety of severe pathologies in
many
tissues. Untreated, these mice live for approximately one week. Treated with
an
antioxidant that does not gain access to the brain, the mice live longer, but
develop a lethal neurological disorder. This disorder, a spongiform
encephalopathy, involves widespread pathological damage to the brain and
profound motor disturbances.
In the Journal of Neuroscience study, mice lacking SOD2 were treated with
three
different SCSs. The SCSs are proprietary compounds developed by Eukarion that
mimic the naturally occurring cellular antioxidant enzymes SOD and catalase.
These antioxidant enzymes normally work together to protect cells and tissues
from damage due to oxidative stress. The study showed that treatment with each
of the SCSs dramatically enhanced survival of the mice, increasing their
lifespan to greater than three-fold that of untreated mice. In addition, SCS
treatment rescued the spongiform neurodegenerative disorder, demonstrating
that
the SCSs crossed the blood-brain barrier and gained access to the
mitochondria,
the main site of oxidative stress.
"These studies are important and relevant to human diseases," said Simon
Melov,
Ph.D., a founding faculty member of the Buck Institute. "They clearly
demonstrate, in a mammalian system, the link between a build-up of
mitochondrial oxidative stress and the development of severe neurodegeneration
with potential relevance to several age-related degenerative diseases.
Further,
they build on previous studies we published which showed a significant
extension of life span in the nematode worm C. elegans through treatment with
SCSs, now extending key elements of those earlier findings to mammals."
"These new results also build upon our earlier research in models for
neurological disorders such as stroke and ALS, demonstrating clearly that SCSs
cross the blood-brain barrier and protect the brain mitochondria from
oxidative
damage," said Susan R. Doctrow, Ph.D., Eukarion's Vice President, Research,
"In
particular, the most effective compound in the study, EUK-189, was designed
for
enhanced cellular and brain permeability. We are working to advance SCSs such
as EUK-189 toward clinical development for treatment of a potentially broad
range of degenerative, age-related conditions."
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Useless hypotheses, etc.:
consciousness, phlogiston, philosophy, vitalism, mind, free will, qualia,
analog computing, cultural relativism, GAC, Cyc, Eliza, cryonics, individual
uniqueness, ego, human values, scientific relinquishment, malevolent AI
We move into a better future in proportion as science displaces superstition.
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