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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 News and Current Multiple Sclerosis Events RSSTrapping white blood cells proves novel strategy against chronic viral infections
Seeing disease-fighting white blood cells vanish from the blood usually signals a weakened immune system. But preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection, researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found.
Trapping white blood cells proves novel strategy against chronic viral infections
Seeing disease-fighting white blood cells vanish from the blood usually signals a weakened immune system. But preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection, researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found.
Protein complementarity may offer new insights into autoimmune diseases
The discovery of "complementary" antibodies against plasminogen in patients with blood vessel inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCAs) may lead to new approaches to research, testing, and treatment of ANCA vasculitis and other autoimmune diseases, suggests a paper in the December Journal of the American Society of Nephrology (JASN).
UNC study: shape, not just size, impacts effectiveness of emerging nanomedicine therapies
In the budding field of nanotechnology, scientists already know that size does matter. But now, researchers at the University of North Carolina at Chapel Hill have shown that shape matters even more - a finding that could lead to new and more effective methods for treating cancer and other diseases, from diabetes and multiple sclerosis to arthritis and obesity.
Multiple Sclerosis: new MRI contrast medium enables early diagnosis in animal model
In an animal model of multiple sclerosis (MS), neuroradiologists and neurologists of the University hospitals of Heidelberg and Würzburg have been able to visualize inflammatory tissue damage, most of which had remained unrecognized up to now, with the aid of a new contrast medium, Gadofluorine M, in magnetic resonance imaging.
New Guidelines for Treating Rheumatoid Arthritis
Proven combinations of medicines and the introduction of new anti-arthritis drugs have significantly improved the treatment of rheumatoid arthritis (RA), according to guidelines issued by the American College of Rheumatology and co-authored by physicians at the University of Alabama at Birmingham (UAB).
Milestone for cannabinoid MS study
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study at the Peninsula Medical School in Plymouth has reached an important milestone with the news that the full cohort of 493 people with multiple sclerosis (MS) has been recruited to the study.
Statins have unexpected effect on pool of powerful brain cells
Cholesterol-lowering drugs known as statins have a profound effect on an elite group of cells important to brain health as we age, scientists at the University of Rochester Medical Center have found. The new findings shed light on a long-debated potential role for statins in the area of dementia.
Best treatment for MS may depend on disease subtype
Animal studies by University of Michigan scientists suggest that people who experience the same clinical signs of multiple sclerosis (MS) may have different forms of the disease that require different kinds of treatment.
Medicines derived from cannabis: a review of adverse events
Researchers at the McGill University Health Centre (MUHC), McGill University and the University of British Columbia (UBC) determined that medical use of cannabinoids do not cause an increase in serious adverse events, but are associated with an increase in some non-serious adverse events.
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