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Department of Medical Research, China Medical
College Hospital, Taiwan
Spinal
muscular atrophy (SMA) is an autosomal recessive
disease characterized by degeneration of the
anterior horn cells of the spinal cord, leading to
muscular paralysis with muscular atrophy. No
effective treatment of this disorder is presently
available. Studies of the correlation between
disease severity and the amount of survival motor
neuron (SMN) protein have shown an inverse
relationship. We report that sodium butyrate
effectively increases the amount of exon
7-containing SMN protein in SMA lymphoid cell lines
by changing the alternative splicing pattern of exon
7 in the SMN2 gene. In vivo, sodium butyrate
treatment of SMA-like mice resulted in increased
expression of SMN protein in motor neurons of the
spinal cord and resulted in significant improvement
of SMA clinical symptoms.
DOES IT RUN IN THE FAMILY ?
When people learn that a family member has a
genetic disorder, they often wonder how this
could be the case if it doesn’t "run in the
family."
The chromosome 5 type of SMA (the most common
type) follows an inheritance pattern known as
autosomal recessive, which often takes
families by surprise. Diseases that are
recessive require two gene flaws — usually
one from each parent, but occasionally one from
one parent and one that occurs as a fetus is
being formed — before the disease shows itself.
People who have only one gene flaw for a
recessive disease are said to be carriers
and usually show no symptoms. Often, a family
has no idea that some members are carriers until
a child is born with a recessive disorder.
The autosomes are the numbered
chromosomes, that is, all the chromosomes except
the X and the Y, which determine gender. If both
parents are carriers of SMN-related SMA, the
risk of each pregnancy producing a child with
the disease is 25 percent. This risk doesn’t
change no matter how many children in the family
have been affected previously. The "dice are
rolled" with each new conception. Genetic
testing for chromosome 5 SMA is widely available
for those suspected of having the disease,
including unborn babies. However, as of 2003,
carrier testing for SMA is more difficult and
not widely available.
Oral administration of
sodium butyrate to intercrosses of heterozygous
pregnant knockout-transgenic SMA-like mice decreased
the birth rate of severe types of SMA-like mice, and
SMA symptoms were ameliorated for all three types of
SMA-like mice. These results suggest that sodium
butyrate may be an effective drug for the treatment
of human SMA patients.
PMID: 11504946 [PubMed - indexed for MEDLINE]
People with SMA are involved in all areas of
society: the arts, science, law, management,
teaching — you name it. Children with SMA tend to be
highly intelligent, creative and adaptable
individuals who contribute much to the world despite
their challenges. |
