It is a mystery why the spine of an otherwise healthy
person would develop a strange twist- one that may
keep worsening at an alarming pace. This has interested
physicians and biologists for several generations.
Many have spent their careers in research of the
etiology - the Greek word meaning "study of
cause." They have done biopsies of muscle,
bone and disc; animal studies were another tool.
Yet the basic truth is still this: we do not
know the cause of most human spinal deformities.
We would certainly like to have a better treatment
for young children than the brace; a better corrective
method than surgery. Understanding the cause is
the first step in finding a cure. The National Scoliosis
Foundation has been instrumental in efforts to find
it. The funding and encouragement provided by the
Foundation has been invaluable. Current work on
etiology involves tracking down promising leads
and using new genetic techniques to take a fresh
Promising leads involve hormones and platelets.
It has been shown that removing the pineal gland
in the brain of some animals produces scoliosis.
Understanding the hormones that this gland produces
may shed an important light on the cause of scoliosis.
Melatonin is one such product; there may be others.
Another clue to the problem may come from platelets.
These are small particles found in blood which help
to produce clotting. They have a contracting protein
called calmodulin which functions like a muscle
and helps pull clots together. This protein shows
promise of predicting which scoliosis may get worse
and which may not. Like other clues, it may lead
us closer to the cause of the curves. The problem
with animal models and other clues is that they
may not necessarily tell what is really happening
in people. Some experts feel that the cause of scoliosis
may rest with genes which are involved with regulating
body order and symmetry throughout life.
Genetic research has the promise of finding the
basic cause of scoliosis. It has helped show the
causes of many conditions, such as Muscular dystrophy
and various tumors. In scoliosis, researchers first
started by looking for abnormalities in several
“candidate genes”: genes which might
logically be thought to cause scoliosis. These involved
several dozen basic building blocks of bone, cartilage,
and ligament. Blood samples were collected from
thousands of persons with scoliosis and their families.
From these, DNA was saved and analyzed. (Figure
1) These did not show any abnormalities.
The next step involved screening the entire genome-
the entire length of the human DNA. Researchers
were looking for areas which were commonly linked
to scoliosis- in other words, which were seen more
commonly in persons with scoliosis than those without.
2) This required several thousand blood samples,
powerful lab tools and a good command of statistics.
Many members of the National Scoliosis Foundation
generously participated in this collection. An example
of a family with an extensive amount of scoliosis
is shown here. (Figure
3) This work is still going on in labs such
as Nancy Miller’s in Baltimore, Carol Wise’s
in Dallas, and Jose Morcuende’s in Iowa City.
Separate work on congenital scoliosis is being carried
out in Philadelphia and Toronto. Interest has risen
since linkage to at least four different chromosomes
has been found. In some families, abnormalities
in the X-chromosome were found. This may explain
some of the gender differences seen in scoliosis.
Much more work needs to be done. These findings
need to be confirmed, and the genes involved need
to be investigated. What we know now is some regions
of chromosomes which may hold the genes. This is
like knowing the state and city of a friend but
not the street and house number. When we find the
gene(s), we need to find what they do. Is there
more than one gene for scoliosis? How does they
cause scoliosis? How can we (safely) intervene?
It is also likely that other genes in each person
may interact with the gene causing scoliosis to
influence the severity of the curve, and explain
why some people develop severe curves and others
do not. The road ahead is farther than that already
traveled. Understanding of the etiology of congenital
scoliosis, or misshapen vertebrae, has advanced
through animal models which have been discovered
to have defects in certain proteins (the notch pathway).
These proteins help to “sculpt” the
spine into shape in the early stages of the embryo.
What does the future hold? Until the etiology is
found, we can only guess how medicine might intervene
with new therapies. It seems quite likely that we
will be able to predict which patients’ scoliosis
will get worse and which will not. Thus we may be
able to save some people from the need to wear a
brace unnecessarily. We may be also be able to predict
whose scoliosis will rapidly worsen and when, and
therefore use more targeted bracing. We may even
be able to give medication which slows the worsening
and eliminates the need for a brace altogether.
A real dream would be a way to make scoliosis better
nonsurgically- to reverse the abnormal growth. This
may be a long way off. Although there is no such
strategy now, a better understanding of the etiology
of scoliosis may awaken physicians to such possibilities.
It is also likely that the understanding of scoliosis
will give us better knowledge of other aspects of
the human skeleton. Research into the etiology of
scoliosis is expensive. The money provided by the
National Scoliosis Foundation and others is a good
start but is only a “seed” to get things
It will require millions of dollars to reach the
stage where findings can be put to use helping people.
Support by the National Institutes of Health (NIH)
will be crucial to this process. So far there has
been virtually NO NIH funding of research into the
etiology of spinal deformity. The NIH realizes that
it can’t fund everything, so it tries to put
its money behind projects which will do the greatest
good. Cancer and heart disease are obvious, worthy
targets. Scoliosis is more of a silent disease.
It is rarely fatal. People with scoliosis tend to
deal with it by themselves, and its impact is not
widely felt outside the family. Yet it affects 2-10
people out of every thousand, to some degree. Only
by making known the burden of this disease will
funding be made available for research into scoliosis
by the NIH. Scientists have salaries to pay, equipment
to buy… money is needed!!! People with scoliosis
are best able to make this known. With the leadership
of the National Scoliosis Foundation, people with
scoliosis can make their wishes for etiology research.
For this reason, the Foundation is launching a grass-roots
campaign to highlight the need for funding of etiology
research. The voice of every person needs to be
Click here to find
out how you can make your voice heard, and change
the course of scoliosis history.