EMBARGOED FOR RELEASE
Wednesday, December 26, 2001
5:00 p.m. EST
Margo Warren or
SPS is characterized by fluctuating muscle rigidity in the trunk and limbs
and a heightened sensitivity to stimuli such as noise, touch, and emotional
distress that can set off muscular spasms. People with SPS are often too disabled
to walk or move, or are afraid to leave the house because of stimuli-triggered
spasms and frequent falls. The incidence of SPS has been estimated at one in
every one million persons, but according to Dr. Dalakas, "the disorder is so
often misdiagnosed as Parkinson's disease, multiple sclerosis, fibromyalgia,
psychosomatic illness, or anxiety and phobia that its actual incidence
is probably much higher."
Researchers have known since the 1980s that people with SPS have elevated
circulating antibodies against a particular enzyme, glutamic acid decarboxylase
(GAD65), involved in the synthesis of γ-aminobutyric acid
(GABA), an inhibitory neurotransmitter that controls muscle movement. Since
GABA modulates the action of the excitatory muscular neurotransmitters, lower
levels of circulating GABA allow the excitatory neurotransmitters to hijack
communications between the brain and the motor system, overstimulating the
muscles into stiffness and spasm.
This link between the neurological symptoms of SPS and a potential immunological
culprit led to several preliminary but successful attempts to treat the symptoms
of the disorder with immuno-modulating therapies, including IVIg. Dr. Dalakas
and his colleagues put this anecdotal evidence to the test by designing a double-blind,
cross-over study that would measure the effect of immunoglobulin therapy versus
placebo in a group of patients with SPS.
The research team selected 16 patients who tested positive for GAD65 antibodies
to receive either IVIg or placebo for 3 months. After a 1-month washout period,
the patients crossed to the alternative therapy. Results were based on a "stiffness
scale" and a "heightened sense scale" devised by Dr. Dalakas and his colleagues
to detect changes in the severity of spasms.
Patients treated with IVIg showed a statistically significant decrease in
symptoms of stiffness and spasm. The scores of the IVIg-randomized patients
dropped significantly from the first month to the fourth, but rebounded when
they crossed to placebo. In the placebo group, scores remained constant for
the first 4 months, and then dropped after crossing to IVIg. Eleven of the
14 patients who finished the study became less stiff and more mobile, and were
able to either walk unassisted, resume work activities, or remain upright without
fear of falling.
The current treatment standard for SPS is diazepam, but according to Dr.
Dalakas, "most patients require such high dosages that they become overly sedated." IVIg
treats symptoms more successfully and comes with no disabling side effects.
The mechanism of action of IVIg is not completely understood. Dalakas proposes
that IVIg either blocks production of GAD65 or somehow neutralizes
the circulating antibodies. What causes SPS is also uncertain. "We don't know
why the body begins to produce these antibodies or how they reach the neuronal
cell," says Dalakas. "It could be a virus, or something else that breaks tolerance
and induces the autoimmune process. What we do know is that we have a strong
indication that SPS is an autoimmune disease. As a result, we may be able to
propose and test additional autoimmune modulators."
The Bayer Corporation and Crescent Health donated part of the IVIg used in
The NINDS, part of the National Institutes of Health in Bethesda, Maryland,
is the nation's leading supporter of biomedical research on the brain and nervous
system. The NINDS is celebrating its 50th anniversary this year.
This release will be posted on EurekAlert! at http://www.eurekalert.org and
on the NINDS website at http://www.ninds.nih.gov/news_and_events/index.htm.