Gene expression levels may reveal stage of Huntington's
disease
August 17, 2005
Laptop Battery Markers could help track response to new therapies,
protective strategies
In other studies, Dr. Spindler has explored the effects of aging and caloric restriction on certain stress genes. One of the things he's found in old age is that stress gene expression seems to increase to a higher level, but that caloric restriction decreases this type of expression. Dr. Spindler's studies suggest that lower levels of stress gene expression may be related to less damage to the kidney and blood vessels during aging.
Thinkpad A survey of the genome of patients with Huntington's Disease
(HD) has identified potential markers of the progression of this
devastating neurological disorder. Researchers from the MassGeneral
Institute for Neurodegenerative Disorders (MIND) found a set of
genes that are expressed at higher levels in blood samples from
people with HD than in samples from controls. The expression of
these genes also rose as the disease progressed from asymptomatic
to symptomatic stage. The study has been published in the August 2
issue of Proceedings of the National Academy of Sciences.
Muscle biopsies and hormone analysis tests were done, art gene chip analysis to measure the expression levels of over 40, 000 genes!
Microsoft "These biomarkers may be valuable in monitoring patients'
response to experimental treatments," says Dimiti Krainc, MD, PhD,
of MIND and the MGH Department of Neurology. "Since these changes
can be seen at the earliest stages of the disease, they may be
particularly helpful in evaluating neuroprotective strategies that
could be applied before symptoms develop."
There are many medical conditions in which increased gene expression would prove beneficial, said lead author Dr. Bethany Janowski, an assistant professor of pharmacology. "In some disease states, it's not that gene expression is completely turned off, but rather, the levels of expression are lower than they should be, " which results in an inadequate amount of a particular protein in the body, Janowski said in a prepared statement.
Laptop Computers HD is an inherited disorder caused by a mutation in the gene for
a protein called huntingtin. Although its normal function has not
yet been discovered, huntingtin is essential for growth and
development. The HD-associated mutation involves excessive
repetition of a specific gene segment, causing an abnormal version
of the protein to accumulate in the brain and destroy brain cells
in an area called the striatum. Symptoms of HD, which usually begin
to appear in the middle years, include uncontrolled movement,
erratic emotions and problems with thinking and memory. Symptoms
worsen over the 10- to 30-year course of the disorder, until
patients die from a variety of complications.
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Laptop Computer Although HD appears to affect only the central nervous system,
mutant huntingtin and proteins it interacts with are found
throughout the body, including blood cells. This suggests that the
mutation may have effects that, while not producing symptoms, could
show up on a blood test. Such a test could provide a more
accessible way to monitor the underlying disease process in the
brain. The MGH team analyzed blood samples from patients with HD,
including asymptomatic carriers of the HD mutation, and compared
their gene expression patterns to those of control
participants.
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Desktop Computer The researchers found hundreds of genes for which expression
levels were significantly altered in HD patients or carriers,
compared with controls, and then identified a set of 12 genes for
which the differences were most significant. In addition,
expression levels in younger presymptomatic carriers of the HD
mutation were closer to those of the controls and rose to
disease-associated levels in carriers approaching the age at which
symptoms usually appear. The investigators then analyzed blood
samples from participants in a Phase 1 trial of a potential HD
treatment and found that four weeks of treatment produced a
significant reduction in expression of the 12-gene set in most
participants.
Notebooks "We need to analyze these findings in a larger phase III
clinical study where changes in gene expression can be correlated
with possible delay in disease onset or progression. Moreover,
further research may identify other combinations of marker genes
that reflect various stages of HD and predict clinical effects of
new experimental treatments," says Krainc. He also notes that the
identified 12-gene set is only one potentially useful biomarker,
and others of the hundreds of genes with altered expression may
also provide critical information in various clinical situations.
Krainc is an assistant professor of Neurology at Harvard Medical
School.
Lenovo Massachusetts General Hospital
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