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'HiCy' drug regimen reverses ms symptoms in selected patients
June 11, 2008New approach to immunosuppressant treatment tested in nine individuals shows promise
A short-term, very-high dose regimen of the immune-suppressing drug cyclophosphamide seems to slow progression of multiple sclerosis (MS) in most of a small group of patients studied and may even restore neurological function lost to the disease, Johns Hopkins researchers report. The findings in nine people, most of whom had failed all other treatments, suggest new ways to treat a disease that tends to progress relentlessly.
"We didn't expect such a dramatic return of function," says Douglas Kerr, M.D., Ph.D, associate professor of neurology at the Johns Hopkins University School of Medicine. "Although we're very early in the game, we think this approach could be the linchpin of a significant advance for MS treatment."
Researchers have used the so called HiCy treatments with some success at Johns Hopkins for a variety of other immune system disorders, including aplastic anemia, lupus and myasthenia gravis.
Cyclophosphamide kills immune-system cells but spares the bone marrow stem cells that make them. The usual method of delivering it in pulsed, small doses, however, can cause the drug to build up to toxic concentrations in patients' bodies, causing a variety of side effects, including a greatly increased risk of infection.
Seeking an alternative way to use the drug, Kerr and his colleagues reasoned that HiCy might clear out the majority of a patient's immune system in one fell swoop, then allow it to "reboot," giving nerve cells a fresh start and an opportunity to repair themselves. In the current study, nine MS patients got a total single infusion of 200 milligrams per kilogram of cyclophosphamide intravenously over four days, a dose several times higher than that given in pulsed regimens but significantly lower than the total amount usually given patients over time.
Before treatment, Kerr says, the study participants were "the worst of the worst" among MS patients. Eight of the nine patients had failed conventional MS treatments, and several of them were wheelchair-bound.
Reporting in the June 9 Archives of Neurology, the Johns Hopkins team said the disease appeared to reverse course for seven of the nine patients over two years following treatments. Overall, the patients, men and women ranging in age from 20 to 47 at the beginning of the study, experienced a 40 percent reduction in scores of a standard test that measures disability. They also had an overall 87 percent improvement in scores on a composite test that measures physical and mental function.
MS, which affects approximately 400,000 people - predominantly women - in the United States, is believed to occur when the body's immune system attacks the insulating sheath that coats nerve cells, causing it to degenerate. Consequently, electrical signals that the cells use to communicate with the rest of the body become progressively weaker, leading to symptoms that include numbness, tingling, cognitive problems and sometimes paralysis.
Researchers have identified four different subtypes of MS, and each is thought to be caused by a different autoimmune process. As a result, developing a treatment that effectively targets all types of MS has been challenging, says Kerr.
Kerr cautions that the "reboot" phenomenon didn't work in all the patients. Two years after treatment, MRI images showed that the disease had reactivated in about half the study participants, suggesting that their renewed ability may not be permanent.
Kerr's colleague Adam Kaplin, M.D., Ph.D., assistant professor of psychiatry and neurology at the Johns Hopkins School of Medicine, is leading efforts to improve HiCy therapy with a blood test in development that could predict which patients would benefit the most from HiCy treatment. Also, since immune cells that regrow after HiCy treatment may contain the same defect that leads to MS, Kaplin and his colleagues are working on a way to regrow only healthy immune cells.
Johns Hopkins Medical Institutions
Researchers have used the so called HiCy treatments with some success at Johns Hopkins for a variety of other immune system disorders, including aplastic anemia, lupus and myasthenia gravis.
Cyclophosphamide kills immune-system cells but spares the bone marrow stem cells that make them. The usual method of delivering it in pulsed, small doses, however, can cause the drug to build up to toxic concentrations in patients' bodies, causing a variety of side effects, including a greatly increased risk of infection.
Seeking an alternative way to use the drug, Kerr and his colleagues reasoned that HiCy might clear out the majority of a patient's immune system in one fell swoop, then allow it to "reboot," giving nerve cells a fresh start and an opportunity to repair themselves. In the current study, nine MS patients got a total single infusion of 200 milligrams per kilogram of cyclophosphamide intravenously over four days, a dose several times higher than that given in pulsed regimens but significantly lower than the total amount usually given patients over time.
Before treatment, Kerr says, the study participants were "the worst of the worst" among MS patients. Eight of the nine patients had failed conventional MS treatments, and several of them were wheelchair-bound.
Reporting in the June 9 Archives of Neurology, the Johns Hopkins team said the disease appeared to reverse course for seven of the nine patients over two years following treatments. Overall, the patients, men and women ranging in age from 20 to 47 at the beginning of the study, experienced a 40 percent reduction in scores of a standard test that measures disability. They also had an overall 87 percent improvement in scores on a composite test that measures physical and mental function.
MS, which affects approximately 400,000 people - predominantly women - in the United States, is believed to occur when the body's immune system attacks the insulating sheath that coats nerve cells, causing it to degenerate. Consequently, electrical signals that the cells use to communicate with the rest of the body become progressively weaker, leading to symptoms that include numbness, tingling, cognitive problems and sometimes paralysis.
Researchers have identified four different subtypes of MS, and each is thought to be caused by a different autoimmune process. As a result, developing a treatment that effectively targets all types of MS has been challenging, says Kerr.
Kerr cautions that the "reboot" phenomenon didn't work in all the patients. Two years after treatment, MRI images showed that the disease had reactivated in about half the study participants, suggesting that their renewed ability may not be permanent.
Kerr's colleague Adam Kaplin, M.D., Ph.D., assistant professor of psychiatry and neurology at the Johns Hopkins School of Medicine, is leading efforts to improve HiCy therapy with a blood test in development that could predict which patients would benefit the most from HiCy treatment. Also, since immune cells that regrow after HiCy treatment may contain the same defect that leads to MS, Kaplin and his colleagues are working on a way to regrow only healthy immune cells.
Johns Hopkins Medical Institutions
Multiple Sclerosis Current Events and Multiple Sclerosis News RSSMultiple health concerns surface as winter, vitamin D deficiences arrive
A string of recent discoveries about the multiple health benefits of vitamin D has renewed interest in this multi-purpose nutrient, increased awareness of the huge numbers of people who are deficient in it, spurred research and even led to an appreciation of it as "nature's antibiotic."
Factors from common human bacteria may trigger multiple sclerosis
Current research suggests that a common oral bacterium may exacerbate autoimmune disease. The related report by Nichols et al, "Unique Lipids from a Common Human Bacterium Represent a New Class of TLR2 Ligands Capable of Enhancing Autoimmunity," appears in the December 2009 issue of The American Journal of Pathology.
Drug studied as possible treatment for spinal injuries
Researchers have shown how an experimental drug might restore the function of nerves damaged in spinal cord injuries by preventing short circuits caused when tiny "potassium channels" in the fibers are exposed.
CSHL team solves structure of NMDA receptor unit that could be drug target for neurological diseases
A team of scientists at Cold Spring Harbor Laboratory (CSHL) reports on Thursday their success in solving the molecular structure of a key portion of a cellular receptor implicated in Alzheimer's, Parkinson's, and other serious illnesses.
Men leave: Separation and divorce far more common when the wife is the patient
A woman is six times more likely to be separated or divorced soon after a diagnosis of cancer or multiple sclerosis than if a man in the relationship is the patient, according to a study that examined the role gender played in so-called "partner abandonment." The study also found that the longer the marriage the more likely it would remain intact.
Neurologists Investigate Possible New Underlying Cause of MS
Neurologists at the University at Buffalo are beginning a research study that could overturn the prevailing wisdom on the cause of multiple sclerosis (MS).
Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
Gentle touch may aid multiple sclerosis patients
While gripping, lifting or manipulating an object such as drinking from a cup or placing a book on a shelf is usually easy for most, it can be challenging for those with neurological diseases such as multiple sclerosis or Parkinson's, or for people who had a stroke. For them, the tight gripping can cause fatigue, making everyday tasks difficult.
Urate in blood and spinal fluid may predict slower decline in patients with Parkinson's disease
Higher concentration of urate (an antioxidant) in the blood and spinal fluid of patients with early Parkinson's disease is associated with slower rates of clinical decline.
Oxidized form of a common vitamin may bring relief for ulcerative colitis
New research published in the Journal of Leukocyte Biology finds retinoic acid may alleviate ulcerative colitis and similar irritable bowel diseases.
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