Mending the Broken
Brain:
Novel Ways to Repair Brain Damage
Using Stem Cells and Genes
Jakob Reiser, Ph.D.
Currently, most treatments to relieve damage to the brain and spinal cord caused by disease or accidents aim to relieve symptoms and limit further damage. But recent research carried out in laboratory animals has raised possibilities for actually repairing nervous system damage and disease.
Diseases
Affecting the Brain
There are a wide variety of diseases
that alter the normal function of
the brain. These include tumors,
genetic defects which often lead
to abnormal brain development and
mental retardation, and several
common brain disorders such as Alzheimer's
disease and Parkinson's disease.
Three percent of the human population
is estimated to be affected by serious
brain diseases. In about one third
of these cases, the cause appears
to be genetic.
Therapies
to Treat Brain Disorders
Owing to the complexity of the brain,
most brain disorders lack effective
treatments and therefore require
the development of novel therapeutic
approaches. Such approaches may
include grafting
to the brain of specific cells (cell-based
therapy) or of therapeutic genes
(gene therapy). Ongoing studies
in experimental animals (mice, rats,
and monkeys) show that these treatments
can relieve disease symptoms. However,
the long-term effects of such interventions
are presently unknown, and because
of ethical reasons it will be a
challenge to extend these procedures
to humans.
Cell-Based
Therapies
Cell-based therapeutic strategies
were originally established in patients
afflicted with Parkinson's disease.
Researchers have developed a way
to treat Parkinson's disease in
adults by injecting into their brains
fetal neural cells that make dopamine,
a brain chemical lacking in Parkinson's.
Although initially quite promising,
this study was recently phased out
because the usefulness of the treatment
was dubious. Compared to patients
not receiving any fetal tissue,
patients who received the fetal
tissue sample showed no significant
benefit in quality of life and absence
of disease.
Brain
Stem Cells
Future cell-based procedures to
repair brain disorders may involve
the transplantation of stem cells.
Stem cells have been harvested from
the brain, bone
marrow, and embryos. Brain stem
cells are rare and difficult to
harvest. Studies carried out in
mice show that such cells have a
high degree of flexibility in terms
of becoming other cells, i.e. they
may turn into different kinds of
brain cells depending on the location
in the brain at which the transplanted
cells arrive. Brain stem cells have
also been isolated from human cadavers,
and their biological features are
being investigated.
Adult
Stem Cells
Bone marrow-derived stem cells are
also referred to as adult stem cells.
Adult stem cells, like all stem
cells, share at least two characteristics.
First, they can make identical copies
of themselves for long periods of
time. Second, they can give rise
to other cell types that have characteristic
shapes and special functions. Adult
stem cells are easily obtained from
the bone marrow of a subject, and
they can be maintained outside of
the normal environment of the bone
marrow in laboratory flasks. Given
the right nutrients and growth conditions,
such cells are capable of multiplying
under these conditions, leading
to large numbers of cells.
Embryonic
Stem Cells
Stem cells can also be obtained
from embryos. These are called
embryonic stem cells. The
embryonic stem cell is derived from
one of the earliest stages of the
development of an embryo called
the blastocyst. Specifically, embryonic
stem cells are derived from the
blastocyst at a stage before it
would implant in the uterine wall.
Embryonic stem cells can self-replicate
and give rise to all cell types
in the body. Embryonic stem cells
are obtained from aborted human
fetuses.
Rebuilding
the Nervous System Using Embryonic
Stem Cells
Future research may show that repairing
the brain could be effective using
neural stem cells grown from embryonic
stem cells.
Research has shown that these stem
cells can be directed to transform
into other types of cells.
Despite the positive outlook, a plan to give federal funding to embryonic stem cell research has been delayed on the President's orders. Some groups oppose the research, because obtaining embryonic stem cells requires the death of a human embryo. These groups believe that adult stem cells, which can be isolated without the death of an embryo, should be studied instead. Many researchers, however, believe that embryonic stem cells hold greater promise for treating disease. A decision on this ethically and politically sensitive issue is expected soon.
Correcting
Brain Disroders Before Birth
Using a technique similar to one
used for Parkinson's disease, researchers
are now exploring ways to correct
brain disorders before birth. However,
the technique, years away from being
ready for human clinical trials,
holds promise for treating diseases
of the brain that develop because
of flawed brain cells. Such an example
would be Tay-Sachs disease, an inherited
enzyme deficiency disorder in which
a child is born normally but develops
brain failure as an infant. The
disorder occurs in about one out
of every 3,600 children born to
European Jewish families and French-Canadian
families. It leads to mental retardation,
blindness, and death by the age
of four. In theory, injections of
healthy neural stem cells could
supplant the cells whose flaws cause
Tay-Sachs and give the brain sufficient
enzymes to develop normally after
birth.
Gene-Based
Therapy
In an alternative approach, genes
can be delivered directly to the
brain or spinal cord by gene transfer.
This procedure involves gene delivery
vehicles, commonly referred
to as vectors.
Vectors
Derived from Viruses
Virus-based gene transfer vectors
have become vehicles of choice for
the delivery of genes to the brain.
This approach takes advantage of
the properties of viruses as gene
transfer agents. Viruses are essentially
parasites that require the functions
of a host cell in order to survive.
They employ either DNA or RNA as
the genetic material to encode
a limited set of virus-specific
functions. Virus-based gene delivery
is highly efficient. Major concerns
with this strategy are related to
safety aspects and stability of
gene correction over time. Initial
studies in laboratory animals have
been promising. Virus-based strategies
involving cancer-destroying genes
have been applied in patients with
brain tumors, but the outcome of these
treatment strategies were disappointing.
However, similar studies carried
out in rats with brain tumors were
very successful. More studies
are required with virus-based gene
delivery strategies in the human
brain to make this approach clinically
useful.
Glossary
Alzheimer's disease: Progressive
dementia in elderly people
Blastocyst: An embryo made up of 30-150 cells
Bone marrow: Tissue in bone cavities containing stem cells, from which red and white blood cells originate
Brain stem cells: Stem cells found in adult brain tissue that can become other cells in the brain
Cell therapy: Delivery of cells to a patient to overcome a genetic abnormality or to combat a disease (e.g. cancer)
Gene therapy: Delivery of a functioning gene into the cells of a patient to correct a genetic abnormality or to provide a new function in a cell (e.g. cancer destroying gene)
Parkinson's disease: Progressive movement disorder
Stem cells: Cells that have the ability to divide indefinitely throughout the life of an organism and to give rise to many of the specialized cells that make up the organism
Tay-Sachs disease: Enzyme deficiency leading to brain failure
Vector: A disabled virus used as a vehicle to transfer genes into cells
How
to Learn More:
http://stemcells.nih.gov/info/scireport/
Contact
Information:
jreise@lsuhsc.edu
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